EP4649089A1 - Treating proteinopathies - Google Patents

Abstract

This document provides methods and materials for treating a mammal (e.g., a human) having, or at risk of developing, a proteinopathy. For example, one or more karyopherin polypeptides (and/or nucleic acids designed to express a karyopherin polypeptide) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy to treat the mammal.

Description

Attorney Docket No.07039-2180WO1 / 2022-349 TREATING PROTEINOPATHIES C^ROSS-R^EFERENCE T^O R^ELATED A^PPLICATIONS This application claims the benefit of U.S. Patent Application Serial No.63/438,449, filed on January 11, 2023. The disclosure of the prior application is considered part of, and is incorporated by reference in, the disclosure of this application. SEQUENCE LISTING This application contains a Sequence Listing that has been submitted electronically as an XML file named “07039-2108WO1_SL.xml.” The XML file, created on December 29, 2023, is 136000 bytes in size. The material in the XML file is hereby incorporated by reference in its entirety. T^ECHNICAL F^IELD This document relates to methods and materials for treating a mammal (e.g., a human) having, or at risk of developing, a proteinopathy. For example, one or more karyopherin polypeptides (and/or nucleic acids designed to express a karyopherin polypeptide) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy to treat the mammal. BACKGROUND INFORMATION Approximately 5.8 million people in the United States age 65 and older live with Alzheimer’s disease. Alzheimer’s disease is a progressive neurologic disorder that causes the brain to shrink (atrophy) and brain cells to die. Alzheimer’s disease is the most common cause of dementia – a continuous decline in thinking, behavioral and social skills that affects a person’s ability to function independently. One of the defining pathological hallmarks of Alzheimer’s disease is the accumulation of insoluble aggregates of tau polypeptides (encoded by a microtubule- associated protein tau (MAPT) gene) inside neuronal cells in the brain (Mudher et al., Acta Neuropathol. Comm., 5(1):99 (2017); and Goedert et al., Annu. Rev. Neurosci., 40:189-210 (2017)). Attorney Docket No.07039-2180WO1 / 2022-349 S^UMMARY This document provides methods and materials for treating a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a proteinopathy associated with aggregation of tau polypeptides). Proteinopathies associated with the aggregation of tau polypeptides can also be referred to as tauopathies. For example, one or more karyopherin polypeptides (e.g., a karyopherin subunit ?1 (KPNB1) polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) to treat the mammal. As demonstrated herein, karyopherin polypeptides and/or fragments of karyopherin polypeptides can reduce neurodegeneration in tauopathies. For example, karyopherin polypeptides and/or fragments of karyopherin polypeptides can prevent tau polypeptides from undergoing pathological phase transition, can reverse formation of insoluble aggregates, can reduce accumulation of aberrant post-translational tau modifications (e.g. hyperphosphorylation), can restore tau solubility and localization, and can restore tau function in the cytoplasm. In some cases, karyopherin polypeptides and/or fragments of karyopherin polypeptides can be used to slow, delay, reverse, or prevent progression of neurodegeneration in the brain of a mammal. In some cases, karyopherin polypeptides and/or fragments of karyopherin polypeptides can be used to slow, delay, reverse, or prevent the development of neurodegeneration in the brain of a mammal. Having the ability to reduce neurodegeneration in tauopathies as described herein (e.g., by administering one or more karyopherin polypeptides and/or fragments thereof and/or nucleic acids designed to express a karyopherin polypeptide and/or a fragment thereof) provides a unique and unrealized opportunity to treat mammal having, or at risk of developing, a tauopathy. In general, one aspect of this document features methods for treating a mammal having a tauopathy. The methods can include, or consist essentially of, administering a KPNB1 polypeptide or a fragment of the KPNB1 polypeptide to a mammal having a tauopathy. The KPNB1 polypeptide or the fragment can be effective to reduce a symptom of the tauopathy. The symptom can be memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, Attorney Docket No.07039-2180WO1 / 2022-349 changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, or dementia. The method can include identifying the mammal as being in need of the KPNB1 polypeptide or the fragment prior to the administering step. The method can include administering the KPNB1 polypeptide to the mammal. The method can include administering the fragment of the KPNB1 polypeptide to the mammal. The fragment of the KPNB1 polypeptide can consist of the amino acid sequence set forth in any one of SEQ ID NOs:7-25. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age- related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy. The methods can include, or consist essentially of, administering a KPNB1 polypeptide or a fragment of the KPNB1 polypeptide to the mammal. The method can include administering the KPNB1 polypeptide to the mammal. The method can include administering the fragment of the KPNB1 polypeptide to the mammal. The fragment of the KPNB1 polypeptide can consist of the amino acid sequence set forth in any one of SEQ ID NOs:7-25. The method can include identifying the mammal as being in need of the KPNB1 polypeptide or the fragment prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, Attorney Docket No.07039-2180WO1 / 2022-349 amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for treating a mammal having a tauopathy. The methods can include, or consist essentially of, administering nucleic acid encoding a KPNB1 polypeptide or a fragment of the KPNB1 polypeptide to a mammal having a tauopathy, where the KPNB1 polypeptide or the fragment is expressed by cells in a brain of the mammal. The KPNB1 polypeptide or the fragment can be effective to reduce a symptom of the tauopathy. The symptom can be memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, or dementia. The method can include identifying the mammal as being in need of the nucleic acid prior to the administering step. The nucleic acid can encode the KPNB1 polypeptide. The nucleic acid can encode the fragment of the KPNB1 polypeptide. The fragment of the KPNB1 polypeptide can consist of the amino acid sequence set forth in any one of SEQ ID NOs:7-25. The nucleic acid can be in the form of a vector. The vector can be an adeno-associated virus (AAV) vector. The vector can be an expression plasmid. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age- related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Attorney Docket No.07039-2180WO1 / 2022-349 Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy. The methods can include, or consist essentially of, administering nucleic acid encoding a KPNB1 polypeptide or a fragment of the KPNB1 polypeptide to the mammal where the KPNB1 polypeptide or the fragment is expressed by cells in a brain of a mammal having a tauopathy. The method can include identifying the mammal as being in need of the nucleic acid prior to the administering step. The nucleic acid can encode the KPNB1 polypeptide. The nucleic acid can encode the fragment of the KPNB1 polypeptide. The fragment of the KPNB1 polypeptide can consist of the amino acid sequence set forth in any one of SEQ ID NOs:7-25. The nucleic acid can be in the form of a vector. The vector can be an AAV vector. The vector can be an expression plasmid. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features uses of a composition including a KPNB1 polypeptide or a fragment of the KPNB1 polypeptide to treat a mammal having a tauopathy. In another aspect, this document features a KPNB1 polypeptide or a fragment of the KPNB1 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. In another aspect, this document features a KPNB1 polypeptide or a fragment of the KPNB1 polypeptide for use in the treatment of a tauopathy. Attorney Docket No.07039-2180WO1 / 2022-349 In another aspect, this document features uses of a composition including nucleic acid encoding a KPNB1 polypeptide or a fragment of the KPNB1 polypeptide to treat a mammal having a tauopathy. In another aspect, this document features nucleic acid encoding a KPNB1 polypeptide or a fragment of the KPNB1 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. In another aspect, this document features nucleic acid encoding a KPNB1 polypeptide or a fragment of the KPNB1 polypeptide for use in the treatment of a tauopathy. In another aspect, this document features methods for treating a mammal having a tauopathy. The methods can include, or consist essentially of, administering an importin-3 (IPO3) polypeptide or a fragment of the IPO3 polypeptide to a mammal having a tauopathy. The method can include administering the IPO3 polypeptide to the mammal. The method can include administering the fragment of the IPO3 polypeptide to the mammal. The fragment of the IPO3 polypeptide can consist of the amino acid sequence set forth in any one of SEQ ID NOs:26-55. The IPO3 polypeptide or the fragment can be effective to reduce a symptom of the tauopathy. The symptom can be memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, or dementia. The method can include identifying the mammal as being in need of the IPO3 polypeptide or the fragment prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease Attorney Docket No.07039-2180WO1 / 2022-349 dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy. The methods can include, or consist essentially of, administering an IPO3 polypeptide or a fragment of the IPO3 polypeptide to the mammal. The method can include administering the IPO3 polypeptide to the mammal. The method can include administering the fragment of the IPO3 polypeptide to the mammal. The fragment of the IPO3 polypeptide can consist of the amino acid sequence set forth in any one of SEQ ID NOs:26-55. The method can include identifying the mammal as being in need of the IPO3 polypeptide or the fragment prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging- related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for treating a mammal having a tauopathy. The methods can include, or consist essentially of, administering nucleic acid encoding an IPO3 polypeptide or a fragment of the IPO3 polypeptide to the mammal, where the IPO3 polypeptide or the fragment is expressed by cells in a brain of a mammal having a tauopathy. The nucleic acid can encode the IPO3 polypeptide. The nucleic acid can encode the fragment of the IPO3 polypeptide. The nucleic acid can be in the form of a vector. The vector can be an AAV vector. The vector can be an expression plasmid. The IPO3 polypeptide can consist of the amino acid sequence set forth in any one of SEQ ID NOs:26- 55. The IPO3 polypeptide or the fragment can be effective to reduce a symptom of the tauopathy. The symptom can be memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, Attorney Docket No.07039-2180WO1 / 2022-349 changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, or dementia. The method can include identifying the mammal as being in need of the nucleic acid prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto- nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy. The methods can include, or consist essentially of, administering nucleic acid encoding an IPO3 polypeptide or a fragment of the IPO3 polypeptide to the mammal where the IPO3 polypeptide or the fragment is expressed by cells in a brain of a mammal having a tauopathy. The method can include identifying the mammal as being in need of the nucleic acid prior to the administering step. The nucleic acid can encode the IPO3 polypeptide. The nucleic acid can encode the fragment of the IPO3 polypeptide. The IPO3 polypeptide can consist of the amino acid sequence set forth in any one of SEQ ID NOs:26-55. The nucleic acid can be in the form of a vector. The vector can be an AAV vector. The vector can be an expression plasmid. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age- Attorney Docket No.07039-2180WO1 / 2022-349 related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features uses of a composition including an IPO3 polypeptide or a fragment of the IPO3 polypeptide to treat a mammal having a tauopathy. In another aspect, this document features an IPO3 polypeptide or a fragment of the IPO3 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. In another aspect, this document features an IPO3 polypeptide or a fragment of the IPO3 polypeptide for use in the treatment of a tauopathy. In another aspect, this document features uses of a composition including nucleic acid encoding an IPO3 polypeptide or a fragment of the IPO3 polypeptide to treat a mammal having a tauopathy. In another aspect, this document features nucleic acid encoding an IPO3 polypeptide or a fragment of the IPO3 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. In another aspect, this document features nucleic acid encoding an IPO3 polypeptide or a fragment of the IPO3 polypeptide for use in the treatment of a tauopathy. In another aspect, this document features methods for treating a mammal having a tauopathy. The methods can include, or consist essentially of, administering an IPO13 polypeptide or a fragment of the IPO13 polypeptide to a mammal having a tauopathy. The method can include administering the IPO13 polypeptide to the mammal. The method can include administering the fragment of the IPO13 polypeptide to the mammal. The fragment of the IPO13 polypeptide can consist of the amino acid sequence set forth in any one of SEQ ID NOs:56-77. The IPO13 polypeptide or the fragment can be effective to reduce a symptom of the tauopathy. The symptom can be memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor Attorney Docket No.07039-2180WO1 / 2022-349 disturbance, ocular apraxia, psychiatric symptoms, or dementia. The method can include identifying the mammal as being in need of the IPO13 polypeptide or the fragment prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy. The methods can include, or consist essentially of, administering an IPO13 polypeptide or a fragment of the IPO13 polypeptide to a mammal having a tauopathy. The method can include administering the IPO13 polypeptide to the mammal. The method can include administering the fragment of the IPO13 polypeptide to the mammal. The fragment of the IPO13 polypeptide can consist of the amino acid sequence set forth in any one of SEQ ID NOs:56-77. The method can include identifying the mammal as being in need of the IPO13 polypeptide or the fragment prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. Attorney Docket No.07039-2180WO1 / 2022-349 In another aspect, this document features methods for treating a mammal having a tauopathy. The methods can include, or consist essentially of, administering nucleic acid encoding an IPO13 polypeptide or a fragment of the IPO13 polypeptide to the mammal, where the IPO13 polypeptide or the fragment is expressed by cells in a brain of the mammal. The nucleic acid can encode the IPO13 polypeptide. The nucleic acid can encode the fragment of the IPO13 polypeptide. The nucleic acid can be in the form of a vector. The vector can be an AAV vector. The vector can be an expression plasmid. The fragment of the IPO13 polypeptide can consist of the amino acid sequence set forth in any one of SEQ ID NOs:56-77. The IPO13 polypeptide or the fragment can be effective to reduce a symptom of the tauopathy. The symptom can be memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, or dementia. The method can include identifying the mammal as being in need of the nucleic acid prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto- nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy. The methods can include, or consist essentially of, administering nucleic acid encoding an IPO13 polypeptide or a fragment of the IPO13 polypeptide to the mammal where the IPO13 polypeptide or the fragment is expressed by cells in a brain of a mammal having a tauopathy. The method can include identifying the Attorney Docket No.07039-2180WO1 / 2022-349 mammal as being in need of the nucleic acid prior to the administering step. The nucleic acid can encode the IPO13 polypeptide. The nucleic acid can encode the fragment of the IPO13 polypeptide. The fragment of the IPO13 polypeptide can consist of the amino acid sequence set forth in any one of SEQ ID NOs:56-77. The nucleic acid can be in the form of a vector. The vector can be an AAV vector. The vector can be an expression plasmid. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features uses of a composition including an IPO13 polypeptide or a fragment of the IPO13 polypeptide to treat a mammal having a tauopathy. In another aspect, this document features an IPO13 polypeptide or a fragment of the IPO13 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. In another aspect, this document features an IPO13 polypeptide or a fragment of the IPO13 polypeptide for use in the treatment of a tauopathy. In another aspect, this document features uses of a composition including nucleic acid encoding an IPO13 polypeptide or a fragment of the IPO13 polypeptide to treat a mammal having a tauopathy. In another aspect, this document features nucleic acid encoding an IPO13 polypeptide or a fragment of the IPO13 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. In another aspect, this document features nucleic acid encoding an IPO13 polypeptide or a fragment of the IPO13 polypeptide for use in the treatment of a tauopathy. Attorney Docket No.07039-2180WO1 / 2022-349 In another aspect, this document features methods for treating a mammal having a tauopathy. The methods can include, or consist essentially of, administering an IPO4 polypeptide or a fragment of the IPO4 polypeptide to a mammal having a tauopathy. The method can include administering the IPO4 polypeptide to the mammal. The method can include administering the fragment of the IPO4 polypeptide to the mammal. The IPO4 polypeptide or the fragment can be effective to reduce a symptom of the tauopathy. The symptom can be memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, or dementia. The method can include identifying the mammal as being in need of the IPO4 polypeptide or the fragment prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto- nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy. The methods can include, or consist essentially of, administering an IPO4 polypeptide or a fragment of the IPO4 polypeptide to a mammal having a tauopathy. The method can include administering the IPO4 polypeptide to the mammal. The method can include administering the fragment of the IPO4 polypeptide to the mammal. The method can include identifying the mammal as being in need of the IPO4 polypeptide or the fragment prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, Attorney Docket No.07039-2180WO1 / 2022-349 progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging- related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for treating a mammal having a tauopathy. The methods can include, or consist essentially of, administering nucleic acid encoding an IPO4 polypeptide or a fragment of the IPO4 polypeptide to a mammal having a tauopathy, where the IPO4 polypeptide or the fragment is expressed by cells in a brain of the mammal. The nucleic acid can encode the IPO4 polypeptide. The nucleic acid can encode the fragment of the IPO4 polypeptide. The nucleic acid can be in the form of a vector. The vector can be an AAV vector. The vector can be an expression plasmid. The IPO4 polypeptide or the fragment can be effective to reduce a symptom of the tauopathy. The symptom can be memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, or dementia. The method can include identifying the mammal as being in need of the nucleic acid prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging- related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Attorney Docket No.07039-2180WO1 / 2022-349 Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy. The methods can include, or consist essentially of, administering nucleic acid encoding an IPO4 polypeptide or a fragment of the IPO4 polypeptide to a mammal having a tauopathy where the IPO4 polypeptide or the fragment is expressed by cells in a brain of the mammal. The method can include identifying the mammal as being in need of the nucleic acid prior to the administering step. The nucleic acid can encode the IPO4 polypeptide. The nucleic acid can encode the fragment of the IPO4 polypeptide. The nucleic acid can be in the form of a vector. The vector can be an AAV vector. The vector can be an expression plasmid. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age- related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features uses of a composition including an IPO4 polypeptide or a fragment of the IPO4 polypeptide to treat a mammal having a tauopathy. In another aspect, this document features an IPO4 polypeptide or a fragment of the IPO4 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. In another aspect, this document features an IPO4 polypeptide or a fragment of the IPO4 polypeptide for use in the treatment of a tauopathy. In another aspect, this document features uses of a composition including nucleic acid encoding an IPO4 polypeptide or a fragment of the IPO4 polypeptide to treat a mammal having a tauopathy. Attorney Docket No.07039-2180WO1 / 2022-349 In another aspect, this document features nucleic acid encoding an IPO4 polypeptide or a fragment of the IPO4 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. In another aspect, this document features nucleic acid encoding an IPO4 polypeptide or a fragment of the IPO4 polypeptide for use in the treatment of a tauopathy. In another aspect, this document features methods for treating a mammal having a tauopathy. The methods can include, or consist essentially of, administering an IPO11 polypeptide or a fragment of the IPO11 polypeptide to a mammal having a tauopathy. The method can include administering the IPO11 polypeptide to the mammal. The method can include administering the fragment of the IPO11 polypeptide to the mammal. The IPO11 polypeptide or the fragment can be effective to reduce a symptom of the tauopathy. The symptom can be memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, or dementia. The method can include identifying the mammal as being in need of the IPO11 polypeptide or the fragment prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto- nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy. The methods can include, or consist essentially of, administering an IPO11 polypeptide or a fragment of the IPO11 polypeptide to Attorney Docket No.07039-2180WO1 / 2022-349 a mammal having a tauopathy. The method can include administering the IPO11 polypeptide to the mammal. The method can include administering the fragment of the IPO11 polypeptide to the mammal. The method can include identifying the mammal as being in need of the IPO11 polypeptide or the fragment prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for treating a mammal having a tauopathy. The methods can include, or consist essentially of, administering nucleic acid encoding an IPO11 polypeptide or a fragment of the IPO11 polypeptide to a mammal having a tauopathy, where the IPO11 polypeptide or the fragment is expressed by cells in a brain of the mammal. The nucleic acid can encode the IPO11 polypeptide. The the nucleic acid can encode the fragment of the IPO11 polypeptide. The nucleic acid can be in the form of a vector. The vector can be an AAV vector. The vector can be an expression plasmid. The IPO11 polypeptide or the fragment can be effective to reduce a symptom of the tauopathy. The symptom can be memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, or dementia. The method can include identifying the mammal as being in need of the nucleic acid prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging- Attorney Docket No.07039-2180WO1 / 2022-349 related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy. The methods can include, or consist essentially of, administering nucleic acid encoding an IPO11 polypeptide or a fragment of the IPO11 polypeptide to the mammal where the IPO11 polypeptide or the fragment is expressed by cells in a brain of the mammal. The method can include identifying the mammal as being in need of the nucleic acid prior to the administering step. The nucleic acid can encode the IPO11 polypeptide. The the nucleic acid can encode the fragment of the IPO11 polypeptide. The nucleic acid can be in the form of a vector. The vector can be an AAV vector. The vector can be an expression plasmid. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features uses of a composition including an IPO4 polypeptide or a fragment of the IPO11 polypeptide to treat a mammal having a tauopathy. In another aspect, this document features an IPO11 polypeptide or a fragment of the IPO11 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. Attorney Docket No.07039-2180WO1 / 2022-349 In another aspect, this document features an IPO11 polypeptide or a fragment of the IPO11 polypeptide for use in the treatment of a tauopathy. In another aspect, this document features uses of a composition including nucleic acid encoding an IPO11 polypeptide or a fragment of the IPO11 polypeptide to treat a mammal having a tauopathy. In another aspect, this document features nucleic acid encoding an IPO11 polypeptide or a fragment of the IPO11 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. In another aspect, this document features nucleic acid encoding an IPO11 polypeptide or a fragment of the IPO11 polypeptide for use in the treatment of a tauopathy. In another aspect, this document features methods for treating a mammal having a tauopathy. The methods can include, or consist essentially of, administering an IPO12 polypeptide or a fragment of the IPO12 polypeptide to a mammal having a tauopathy. The method can include administering the IPO12 polypeptide to the mammal. The method can include administering the fragment of the IPO12 polypeptide to the mammal. The IPO4 polypeptide or the fragment can be effective to reduce a symptom of the tauopathy. The symptom can be memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, or dementia. The method can include identifying the mammal as being in need of the IPO12 polypeptide or the fragment prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto- nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary Attorney Docket No.07039-2180WO1 / 2022-349 tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy. The methods can include, or consist essentially of, an IPO12 polypeptide or a fragment of the IPO12 polypeptide to a mammal having a tauopathy. The method can include administering the IPO12 polypeptide to the mammal. The method can include administering the fragment of the IPO12 polypeptide to the mammal. The method can include identifying the mammal as being in need of the IPO12 polypeptide or the fragment prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging- related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for treating a mammal having a tauopathy. The methods can include, or consist essentially of, administering nucleic acid encoding an IPO12 polypeptide or a fragment of the IPO12 polypeptide to a mammal having a tauopathy, where the IPO12 polypeptide or the fragment is expressed by cells in a brain of the mammal. The nucleic acid can encode the IPO12 polypeptide. The nucleic acid can encode the fragment of the IPO12 polypeptide. The nucleic acid can be in the form of a vector. The vector can be an AAV vector. The vector can be an expression plasmid. The IPO12 polypeptide or the fragment can be effective to reduce a symptom of the tauopathy. The symptom can be memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow Attorney Docket No.07039-2180WO1 / 2022-349 and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, or dementia. The method can include identifying the mammal as being in need of the nucleic acid prior to the administering step. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging- related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. In another aspect, this document features methods for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy. The methods can include, or consist essentially of, administering nucleic acid encoding an IPO12 polypeptide or a fragment of the IPO12 polypeptide to a mammal having a tauopathy where the IPO12 polypeptide or the fragment is expressed by cells in a brain of the mammal. The method also can include identifying the mammal as being in need of the nucleic acid prior to the administering step. The nucleic acid can encode the IPO12 polypeptide. The nucleic acid can encode the fragment of the IPO12 polypeptide. The nucleic acid can be in the form of a vector. The vector can be an AAV vector. The vector can be an expression plasmid. The mammal can be a human. The tauopathy can be Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging- related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, or primary age-related tauopathy. The tauopathy can be a secondary tauopathy such as Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. The administering can include intracerebral injection. Attorney Docket No.07039-2180WO1 / 2022-349 In another aspect, this document features uses of a composition including an IPO12 polypeptide or a fragment of the IPO12 polypeptide to treat a mammal having a tauopathy. In another aspect, this document features an IPO12 polypeptide or a fragment of the IPO12 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. In another aspect, this document features an IPO12 polypeptide or a fragment of the IPO12 polypeptide for use in the treatment of a tauopathy. In another aspect, this document features uses of a composition including nucleic acid encoding an IPO12 polypeptide or a fragment of the IPO12 polypeptide to treat a mammal having a tauopathy. In another aspect, this document features nucleic acid encoding an IPO12 polypeptide or a fragment of the IPO12 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. In another aspect, this document features nucleic acid encoding an IPO12 polypeptide or a fragment of the IPO12 polypeptide for use in the treatment of a tauopathy. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used to practice the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. DESCRIPTION OF THE DRAWINGS Figures 1A-1B contain schematics of KPNB1 polypeptides and fragments thereof. Figure 1A contains a schematic domain structure of the N-terminal half (HEAT repeats 1-9, Attorney Docket No.07039-2180WO1 / 2022-349 H1-9) and C-terminal half (HEAT repeats 10- 19, H10-19) of KPNB1. Figure 1B contains a schematic domain structure of KPNB1 H1-8mNIS harboring four missense mutations (I178A, F217A, Y255A, I263R) in the nucleoporin-interacting site (NIS). Figures 2A-2D show that a subset of karyopherins that belong to the protein family of ?-importins can reduce aggregation of tau polypeptides. Figure 2A contains an image of a western blot of tau polypeptides in HEK293T lysates co-transfected with expression plasmids encoding GFP-tagged tau polypeptide harboring patient-derived mutations (A152T, P301L, and S320F mutations) that cause it to form pathological hyperphosphorylated amyloid-like aggregates (GFP-Tau^3xMUT) and mCherry-tagged ?-importin polypeptides. Levels of tau polypeptides in the detergent-insoluble fraction were visualized using an anti- GFP antibody and phospho-tau polypeptides were detected with a phospho-tau specific antibody (AT8). Figure 2B contains a graph of the quantification of the western blot of detergent-insoluble tau polypeptide levels standardized to control levels in samples co- transfected with red fluorescent protein mCherry (mCh) alone, shown as a percentage. The graph shows changes of the percent of detergent-insoluble tau polypeptide when cells were co-transfected with various mCherry-tagged ?-importins across three independent experimental replicates. Figure 2C contains an image of a western blot analysis of the detergent-soluble tau polypeptide fraction visualized using anti-GFP. Figure 2D contains a graph of the quantification of the western blot of the soluble tau polypeptide fraction standardized to mCh alone co-transfected samples as control levels, shown as a percentage. The graph shows changes of soluble GFP-Tau^3xMUT polypeptide levels in cells co-transfected with various ?-importins. Radioimmunoprecipitation assay (RIPA) lysis buffer was used to determine detergent solubility. Figure 3 shows that expression of GFP-Tau^3xMut polypeptides causes mislocalization of specific endogenous nucleoporins Nup98 and Nup62 that harbor phenylalanine-glycine (FG) repeat motifs (FG-Nups). HEK293T cells were transfected with expression constructs for GFP-tagged Tau^3xMut polypeptides. Immunofluorescence staining with antibodies against Nup98 and Nup62 show diffuse cytoplasmic mislocalization (Nup62) and/or accumulation of endogenous FG-Nups into perinuclear foci (arrows – Nup98), as compared to the localization in the nuclear envelope found in untransfected cells. Attorney Docket No.07039-2180WO1 / 2022-349 Figures 4A-4B show that organotypic mouse brain slice cultures (BSCs) transduced with adeno-associated virus (AAV) particles to deliver EGFP-Tau^3xMut expression constructs can be used to model tau pathology. Figure 4A shows that overexpression of mutant tau polypeptides causes the formation of abnormal fibrillar inclusions that were positive for phospho-tau (AT8). Nuclei were labeled with the DNA stain DAPI. Figure 4B shows that tau polypeptide inclusions were also positive for an amyloid-specific dye (Amylo-Glo). Nuclei were labeled with the DNA stain DRAQ5. Figures 5A-5C show that overexpressed wild type (WT) tau polypeptides do not cause pathological Amylo-Glo-positive tau polypeptide inclusions. Figure 5A is a schematic of an exemplary BSC transduction experiment that was used to assess tau polypeptide inclusions. Figure 5B contains an image of cells that were transduced with AAV constructs encoding mutant tau polypeptides or WT tau polypeptides. Cells transduced with AAV- Tau^3xMut EGFP, but not AAV-Tau^WT-EGFP, formed amyloid-like Amylo-Glo-positive tau inclusions. Results shown were at 20 days in vitro (DIV). Figure 5C contains an image of a western blot analysis showing the presence of hyperphosphorylated tau positive for the phospho-tau antibody AT8 in cells transduced with AAV-Tau^3xMut EGFP, but not AAV- Tau^WT-EGFP in both the detergent-soluble fraction and the insoluble fraction. Figures 6A-6B shows pathological tau fibrils isolated from brain samples from Alzheimer’s disease patients. Figure 6A contains an image of an electron microscopy analysis of an exemplary Alzheimer’s disease brain sample showing sarkosyl-insoluble tau polypeptides in the form of paired helical filaments. Figure 6B contains an image of a western blot analysis for phospho-tau (AT8) that is present in exemplary Alzheimer’s disease brain samples but absent in control brains. Figures 7A-7B show that tau polypeptide fibrils isolated from Alzheimer’s disease patient brains can be used as seeds to induce tau pathology in cultured cells. Figure 7A contains a schematic of an exemplary method for seeding-dependent tauopathy experiments. Figure 7B contains an image of an immunofluorescence analysis showing that adding sarkosyl-insoluble tau polypeptide fibrils to the Tau RD P301S biosensor reporter cell line, caused the accumulation of fluorescent protein-tagged tau fragments into aggregates. Attorney Docket No.07039-2180WO1 / 2022-349 Figure 8 shows that full length IPO13 polypeptide and C-terminal fragments of an IPO13 polypeptide reduced tau aggregation pathology more than N-terminal fragments of an IPO13 polypeptide. Western blotting was performed to analyze lysates of HEK293T cells co- transfected with an expression plasmid encoding GFP-tagged human wildtype tau and an expression plasmid encoding mCherry (mch), co-transfected with an expression plasmid encoding a triple mutant Tau (Tau 3x) and an expression plasmid encoding mCherry, co- transfected with an expression plasmid encoding Tau 3x and an expression plasmid encoding an mCherry-tagged IPO13 polypeptide, or co-transfected with an expression plasmid encoding Tau 3x and an expression plasmid encoding an mCherry-tagged fragment of an IPO13 polypeptide. Levels of tau protein were visualized 48 hours after transfection using anti-GFP antibody, and phospho-tau (pTau) was labeled with an AT8 antibody. Beta-actin staining was used for normalization. Shown here is the quantification of the western blots from 3 biological replicates. Full length IPO13 (H1-20) and its most active fragments H11- 20, H7-20, and H7-20 are indicated with arrows. Figure 9 shows that specific fragments of an IPO13 polypeptide reduced accumulation of hyperphosphorylated tau aggregates. Immunocytochemistry was performed to analyze HEK293T cells co-transfected with an expression plasmid encoding a GFP-tagged human wildtype Tau polypeptide and an expression plasmid encoding mCherry, co- transfected with an expression plasmid encoding a GFP-tagged triple mutant Tau (Tau 3x) and an expression plasmid encoding mCherry, co-transfected with an expression plasmid encoding a GFP-tagged Tau 3x and an expression plasmid encoding a mCherry-tagged IPO13 polypeptide, or co-transfected with an expression plasmid encoding a GFP-tagged Tau 3x and an expression plasmid encoding an mCherry-tagged fragment of an IPO13 polypeptide (H7-20, H9-20, and H11-20 fragments). Levels of tau protein were visualized 48 hours after transfection using anti phospho-tau antibody (AT8). Fluorescence microscopy shows strongly reduced phospho-tau staining (AT8) when a full-length IPO13 polypeptide and C-terminal IPO13 fragments were expressed. Figure 10 shows that expression of KPNB1, IPO4, and IPO13 reduced seeded tau aggregation in cultured cells. Immunofluorescence images of the Tau RD P301 reporter cell line following seeding with AD-derived tau seeds and transfection with an expression Attorney Docket No.07039-2180WO1 / 2022-349 plasmid encoding mCherry or transfection with an expression plasmid encoding an mCherry- tagged nuclear-import receptor (NIR) polypeptides. Freshly sonicated human AD brain derived seeds caused the formation of YFP-tau aggregates in cells that also express mCherry. Co-transfection with a KPNB1 polypeptide, an IPO4 polypeptide, and an IPO13 polypeptide reduced seeded tau aggregation pathology. Figures 11A and 11B show that expression of KPNB1, IPO4, IPO13, and the C- terminal IPO13 fragment from HEAT repeat 11-20 (H11-20) can reduce seeded tau aggregation in cultured cells. Figure 11A shows immunofluorescence images of Tau RD P301 cells that were treated with AD-derived tau seeds and an expression plasmid encoding mCherry or an expression plasmid encoding an mCherry-tagged NIR. Freshly sonicated human AD brain derived seeds caused the formation of YFP-tau aggregates in cells that also express mCherry. Co-transfection with an expression plasmid encoding an mCherry-tagged KPNB1 polypeptide, an expression plasmid encoding an mCherry-tagged IPO4 polypeptide, an expression plasmid encoding an mCherry-tagged IPO13 polypeptide, or an expression plasmid encoding an mCherry-tagged fragment of an IPO13 polypeptide reduced the seeded tau aggregation pathology. The C-terminal fragment mCherry-IPO13 H11-20 was more active than the N-terminal H1-10. Figure 11B shows immunofluorescence images of Tau RD P301 cells that were transfected with an expression plasmid encoding mCherry or an expression plasmid encoding an mCherry-tagged NIR without any added tau seeds. In the absence of added tau seeds, the Tau RD P301 did not form YFP-positive tau aggregates. Figure 12 shows a schematic of the IPO13 polypeptide, denoting the 20 HEAT repeat regions (H1-20). Figure 13 shows that C-terminal fragments of an IPO13 polypeptide reduced tau aggregation pathology. Western blotting was performed to analyze lysates of HEK293T cells co-transfected with an expression plasmid encoding GFP-tagged human wildtype tau and an expression plasmid encoding mCherry (m-cherry), co-transfected with an expression plasmid encoding a triple mutant Tau (Tau 3x) and an expression plasmid encoding mCherry (m- cherry), co-transfected with an expression plasmid encoding Tau 3x and an expression plasmid encoding an mCherry-tagged IPO13 polypeptide (mch-IPO13), or co-transfected with an expression plasmid encoding Tau 3x and an expression plasmid encoding an Attorney Docket No.07039-2180WO1 / 2022-349 mCherry-tagged C-terminal fragment of an IPO13 polypeptide encoding specific HEAT repeats (e.g. mCherry fused to IPO13 HEAT repeats 5-20 = mch-IPO135-20). Levels of detergent insoluble tau protein were visualized 48 hours after transfection using anti-GFP antibody (top row), and phospho-tau (pTau) was labeled with an AT8 antibody (middle row). Protein levels for Tau 3x + mCherry co-transfections were set to 100% to normalize between biological replicates. Beta-actin staining was used for normalization to protein levels (bottom row). Shown here is the quantification of the western blots from 4 biological replicates. D^ETAILED D^ESCRIPTION This document provides methods and materials for treating a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy). For example, one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) to treat the mammal. In some cases, the methods and materials described herein can be used to treat a proteinopathy (e.g., a tauopathy). For example, one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be administered to a mammal (e.g., a human) in need thereof (e.g., a human having, or at risk of developing, a proteinopathy such as a tauopathy) to slow, delay, reverse, or prevent progression of a proteinopathy (e.g., a tauopathy). In some cases, one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be administered to a mammal (e.g., a human) in need thereof (e.g., a human having, or at risk of developing, a proteinopathy such as a tauopathy) to slow, delay, reverse, or prevent the development of a proteinopathy (e.g., a tauopathy). In some cases, the methods and materials described herein can be used to reduce or eliminate one or more symptoms of a proteinopathy (e.g., a tauopathy). For example, one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or Attorney Docket No.07039-2180WO1 / 2022-349 nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be administered to a mammal (e.g., a human) in need thereof (e.g., a human having, or at risk of developing, a proteinopathy such as a tauopathy) to reduce or eliminate one or more symptoms of a proteinopathy (e.g., a tauopathy). Examples of symptoms of a proteinopathy (e.g., a tauopathy) include, without limitation, memory impairment (e.g., difficulty remembering recent events, difficultly remembering conversations, forgetting the names of family members, and forgetting the names of everyday objects), problems with language ability (e.g., having trouble finding the right words to identify objects, express thoughts, or take part in conversations), cognitive decline, disorientation (e.g., getting lost and misplacing possessions), mood swings, social withdrawal, lethargy, disinhibition, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. In some cases, the materials and methods described herein can be used to reduce the severity of one or more symptoms of a proteinopathy (e.g., a tauopathy) in a mammal (e.g., a human) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, the methods and materials described herein can be used to reduce or eliminate neurodegeneration associated with a proteinopathy (e.g., a tauopathy). For example, one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be administered to a mammal (e.g., a human) in need thereof (e.g., a human having, or at risk of developing, a proteinopathy such as a tauopathy) to slow, delay, reverse, or prevent progression of neurodegeneration associated with a proteinopathy (e.g., a tauopathy). In some cases, one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be administered to a mammal (e.g., a human) in need thereof (e.g., a human having, or at risk of developing, a proteinopathy such as a tauopathy) to slow, delay, Attorney Docket No.07039-2180WO1 / 2022-349 reverse, or prevent the development of neurodegeneration associated with a proteinopathy (e.g., a tauopathy). In some cases, the methods and materials described herein can be used to reduce or eliminate aggregation of tau polypeptides (e.g., pathological aggregation of tau polypeptides such as hyperphosphorylated tau polypeptides). For example, the materials and methods described herein can be used to reduce the number of tau polypeptide aggregates present within the brain of a mammal having a proteinopathy (e.g., a tauopathy) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. For example, the materials and methods described herein can be used to reduce the size (e.g., volume) of one or more tau polypeptide aggregates present within a mammal having a proteinopathy (e.g., a tauopathy) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, the methods and materials described herein can be used to reduce or eliminate one or more post-translational modifications (e.g., phosphorylation) of tau polypeptides (e.g., pathological hyperphosphorylation tau polypeptides). For example, the materials and methods described herein can be used to reduce aberrant post-translational modifications (e.g., hyperphosphorylation) of tau polypeptides present within the brain of a mammal having a proteinopathy (e.g., a tauopathy) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. For example, the materials and methods described herein can be used to reduce phosphorylation of one or more of residues Thr181, Ser199, Ser202, Thr205, Thr212, Ser214, Thr217, Thr231, Ser235, Ser262, Ser396, Ser404, Ser413, and Ser422 of tau polypeptides present within the brain of a mammal having a proteinopathy (e.g., a tauopathy) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, the methods and materials described herein can be used to reduce or eliminate misfolding of tau polypeptides (e.g., misfolding of tau polypeptides into conformations associated with pathological aggregation). For example, the materials and methods described herein can be used to reduce the amount of misfolded tau polypeptides present within the brain of a mammal having a proteinopathy (e.g., a tauopathy) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, the methods and materials described herein can be used to increase the solubility of tau polypeptides (e.g., the percentage of detergent-soluble tau polypeptides). For Attorney Docket No.07039-2180WO1 / 2022-349 example, the materials and methods described herein can be used to increase the solubility of tau polypeptides present within the brain of a mammal having a proteinopathy (e.g., a tauopathy) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, the methods and materials described herein can be used to decrease the solubility of tau polypeptides (e.g., the percentage of detergent-insoluble tau polypeptides). For example, the materials and methods described herein can be used to decrease the solubility of tau polypeptides present within the brain of a mammal having a proteinopathy (e.g., a tauopathy) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, the methods and materials described herein can be used to reduce or eliminate cell death associated with a proteinopathy (e.g., a tauopathy). For example, the materials and methods described herein can be used to reduce the number of apoptotic cells present within the brain of a mammal having a proteinopathy (e.g., a tauopathy) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, the methods and materials described herein can be used to restore cellular localization of tau polypeptides. For example, the materials and methods described herein can be used to increase the number of tau polypeptides that can associate with microtubules within the cytoplasm of cells present within the brain of a mammal having a proteinopathy (e.g., a tauopathy) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. Any appropriate mammal having, or at risk of developing, a proteinopathy (e.g., a tauopathy) can be treated as described herein (e.g., by administering one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof). Examples of mammals that can be treated as described herein include, without limitation, humans, non-human primates such as monkeys, dogs, cats, horses, cows, pigs, sheep, goats, camels, mice, rats, rabbits, hamsters, guinea pigs, and ferrets. When treating a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) as described herein (e.g., by administering one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) Attorney Docket No.07039-2180WO1 / 2022-349 and/or a fragment thereof), the proteinopathy can be any type of proteinopathy. In some cases, a proteinopathy be a tauopathy (e.g., can include aggregation of tau polypeptides). In some cases, a proteinopathy be a synucleinopathy (e.g., can include aggregation of ?- synuclein polypeptides). In some cases, a proteinopathy be a secondary tauopathy (e.g., can include aggregation of tau polypeptides and can include aggregation of one or more other polypeptides such as amyloid polypeptides and/or ?-synuclein polypeptides). In some cases, a proteinopathy can be a neurodegenerative disease. Examples of types of proteinopathies that can be treated as described herein include, without limitation, Alzheimer’s disease (AD), frontotemporal dementia (FTD), Pick's disease (PiD), progressive supranuclear palsy (PSP), argyrophilic grain disease (AGD), globular glial tauopathy (GGT), aging-related tau astrogliopathy (ARTAG), Richardson's syndrome, corticobasal degeneration (CBD), dementia pugilistica, chronic traumatic encephalopathy (CTE), amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) of Guam, frontotemporal dementia parkinsonism linked to chromosome 17 (FTDP-17), Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration (PPND), primary age-related tauopathy (PART), Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies. In some cases, a mammal (e.g., a human) can be identified as having, or as being at risk of developing, a proteinopathy (e.g., a tauopathy). Any appropriate method can be used to identify a mammal (e.g., a human) as having, or as being at risk of developing, a proteinopathy (e.g., a tauopathy). For example, genetic testing, imaging techniques (e.g., brain scanning techniques such as magnetic resonance imaging (MRI), computed tomography (CT) scanning, fluorodeoxyglucose positron emission tomography (FDG-PET) scanning, and SPECT (single proton emission CT) scanning) and/or detection of biomarkers (e.g., via methods such as enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), cerebrospinal fluid real-time quaking-induced conversion (RT- QuIC), single molecule array (Simoa) western blot analysis, single molecule counting (SMC), proximity extension assay (OLINK), and/or mass spectrometry) can be used to identify a mammal as having, or as being at risk of developing, a proteinopathy (e.g., a tauopathy). Attorney Docket No.07039-2180WO1 / 2022-349 Once identified as having, or as being at risk of developing, a proteinopathy (e.g., a tauopathy), the mammal (e.g., the human) can be administered, or instructed to self- administer, one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) as described herein. Any appropriate karyopherin polypeptide and/or fragment thereof (and/or nucleic acid designed to express a karyopherin polypeptide or a fragment thereof) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) as described herein. In some cases, a karyopherin polypeptide can be a modified karyopherin polypeptide. For example, a karyopherin polypeptide that can be used as described herein can be a karyopherin polypeptide that is modified as compared to a naturally existing karyopherin polypeptide (e.g., modified to have increased ability to reduce at least some tau polypeptide aggregation). In some cases, a karyopherin polypeptide can be a beta-karyopherin type karyopherin polypeptide. In some cases, a karyopherin polypeptide can be an alpha-karyopherin type karyopherin polypeptide. In some cases, a karyopherin polypeptide can be an importin (e.g., can have importin functions). In some cases, a karyopherin polypeptide can be an exportin (e.g., can have exportin functions). In some cases, a karyopherin polypeptide can be a biportin (e.g., can have both importin and exportin functions). Examples of karyopherin polypeptides that can be used as described herein include, without limitation, KPNB1 polypeptides, importin (IPO) 3A polypeptides, IPO3B polypeptides, IPO4 polypeptides (also referred to as Ran-binding protein (RANBP) 4 polypeptides), IPO11 polypeptides (also referred to as RANBP11 polypeptides), IPO12 polypeptides (also referred to as transportin 3 (TNPO3) polypeptides), and IPO13 polypeptides (also referred to as RANBP13 polypeptides). When a karyopherin polypeptide is a KPNB1 polypeptide, any appropriate KPNB1 polypeptide (and/or nucleic acid designed to express a KPNB1 polypeptide) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) as described herein. Examples of KPNB1 polypeptides and nucleic acids encoding KPNB1 polypeptides that can be used as described herein include, without limitation, those set forth in the National Center for Biotechnology Information (NCBI) Attorney Docket No.07039-2180WO1 / 2022-349 databases at, for example, accession no. NP_002256 (version NP_002256.2), accession no. NM_002265 (version NM_002265.6), accession no. NP_001263382 (version NP_001263382.1), and accession no. NM_001276453 (version NM_001276453.2).. In some cases, a KPNB1 polypeptide that can be used as described herein can have an amino acid sequence set forth in SEQ ID NO:1 (see, e.g., Example 1). In some cases, a nucleic acid encoding a KPNB1 polypeptide that can be used as described herein can have a nucleotide sequence set forth in SEQ ID NO:2 (see, e.g., Example 1). When a fragment of a karyopherin polypeptide is a KPNB1 polypeptide fragment, any appropriate KPNB1 polypeptide fragment (and/or nucleic acid designed to express a KPNB1 polypeptide fragment) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) as described herein. In some cases, a KPNB1 polypeptide fragment can be derived from the amino acid sequence set forth in SEQ ID NO:1. For example, a KPNB1 polypeptide fragment can be derived from the amino acid sequence of SEQ ID NO:1, and can retain at least some function of a naturally-occurring KPNB1 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). A KPNB1 polypeptide fragment can include at least one of the HEAT repeats present in a KPNB1 polypeptide (e.g., consecutive or non-consecutive HEAT repeats). For example, a KPNB1 polypeptide fragment can include from about 1 HEAT repeat to about 19 HEAT repeats (e.g., from about 1 to about 15, from about 1 to about 12, from about 1 to about 10, from about 1 to about 7, from about 1 to about 5, from about 3 to about 19, from about 5 to about 19, from about 8 to about 19, from about 12 to about 19, from about 15 to about 19, from about 3 to about 15, from about 5 to about 12, from about 3 to about 5, from about 5 to about 8, from about 8 to about 12, or from about 12 to about 15 HEAT repeats) provided that it maintains at least some function of a naturally-occurring KPNB1 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). Attorney Docket No.07039-2180WO1 / 2022-349 A KPNB1 polypeptide fragment can be any appropriate length (e.g., can include any number of amino acids) provided that it maintains at least some function of a naturally- occurring KPNB1 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). For example, a KPNB1 polypeptide fragment can be from about 30 amino acids in length to about 900 amino acids in length (e.g., from about 30 amino acids to about 850 amino acids, from about 30 amino acids to about 800 amino acids, from about 30 amino acids to about 750 amino acids, from about 30 amino acids to about 700 amino acids, from about 30 amino acids to about 650 amino acids, from about 30 amino acids to about 600 amino acids, from about 30 amino acids to about 550 amino acids, from about 30 amino acids to about 500 amino acids, from about 30 amino acids to about 450 amino acids, from about 30 amino acids to about 400 amino acids, from about 30 amino acids to about 350 amino acids, from about 30 amino acids to about 300 amino acids, from about 30 amino acids to about 250 amino acids, from about 30 amino acids to about 200 amino acids, from about 30 amino acids to about 150 amino acids, from about 30 amino acids to about 100 amino acids, from about 50 amino acids to about 900 amino acids, from about 100 amino acids to about 900 amino acids, from about 150 amino acids to about 900 amino acids, from about 200 amino acids to about 900 amino acids, from about 250 amino acids to about 900 amino acids, from about 300 amino acids to about 900 amino acids, from about 350 amino acids to about 900 amino acids, from about 400 amino acids to about 900 amino acids, from about 450 amino acids to about 900 amino acids, from about 500 amino acids to about 900 amino acids, from about 550 amino acids to about 900 amino acids, from about 600 amino acids to about 900 amino acids, from about 650 amino acids to about 900 amino acids, from about 700 amino acids to about 900 amino acids, from about 750 amino acids to about 900 amino acids, from about 800 amino acids to about 900 amino acids, from about 50 amino acids to about 800 amino acids, from about 100 amino acids to about 700 amino acids, from about 200 amino acids to about 600 amino acids, from about 300 amino acids to about 500 amino acids, from about 100 amino acids to about 300 amino acids, from about 200 amino acids to about 400 amino acids, from about 400 amino acids to about 600 amino acids, from about 500 amino acids to about 700 amino acids, or Attorney Docket No.07039-2180WO1 / 2022-349 from about 600 amino acids to about 800 amino acids in length) provided that it maintains at least some function of a naturally-occurring KPNB1 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). In some cases, a KPNB1 polypeptide fragment can comprise, consist essentially of, or consist of an amino acid sequence set forth in Table 1. Table 1. Exemplary KPNB1 polypeptide fragments. Truncation Polypeptide Sequence SEQ ID NO: Attorney Docket No.07039-2180WO1 / 2022-349 o acid sequence set forth in any one of SEQ ID NOs:7-16 with zero, one, two three, or more (e.g., five, eight, 12, 15, 18, 20, 25, 30, 35, 40, or more) amino acid substitutions (e.g., one or more K?R substitutions) within the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:7-16), with zero, one, two, three, four, or five amino acid residues preceding the articulated sequence of the sequence identifier (e.g., any one of SEQ ID Attorney Docket No.07039-2180WO1 / 2022-349 NOs:7-16), and/or with zero, one, two, three, four, or five amino acid residues following the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:7-16), provided that the KPNB1 polypeptide fragment retains at least some activity exhibited by a naturally- occurring KPNB1 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). Examples of such KPNB1 polypeptide fragments can be those set forth in Table 2. Table 2. Exemplary KPNB1 polypeptide fragments. Polypeptide Sequence SEQ ID NO: Attorney Docket No.07039-2180WO1 / 2022-349 When an importin polypeptide is an IPO3 polypeptide (also referred to as a transportin-2 (TNPO2) polypeptide), any appropriate IPO3 polypeptide (and/or nucleic acid designed to express an IPO3 polypeptide) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) as described herein. Examples of IPO3 polypeptides and nucleic acids encoding IPO3 polypeptides include, without limitation, those set forth in the NCBI databases at, for example, accession no. NP_001129668 (version NP_001129668.1), accession no. NM_001136196 (version NM_001136196.2), accession no. NP_038461 (version NP_038461.2), and accession no. NM_013433 (version NM_013433.5). In some cases, an IPO3 polypeptide can have an amino acid sequence set forth in SEQ ID NO:3 (see, e.g., Example 2). In some cases, a nucleic acid encoding an IPO3 polypeptide can have a nucleotide sequence set forth in SEQ ID NO:4 (see, e.g., Example 2). When a fragment of an importin polypeptide is an IPO3 polypeptide fragment, any appropriate IPO3 polypeptide fragment (and/or nucleic acid designed to express an IPO3 polypeptide fragment) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) as described herein. In some cases, an IPO3 polypeptide fragment can be derived from the amino acid sequence set forth in SEQ ID NO:3. An IPO3 polypeptide fragment can include at least one of the HEAT repeats present in an IPO3 polypeptide (e.g., consecutive or non-consecutive HEAT repeats). For example, Attorney Docket No.07039-2180WO1 / 2022-349 an IPO3 polypeptide fragment can include from about 1 HEAT repeat to about 20 HEAT repeats (e.g., from about 1 to about 15, from about 1 to about 12, from about 1 to about 10, from about 1 to about 8, from about 1 to about 5, from about 3 to about 20, from about 5 to about 20, from about 7 to about 20, from about 10 to about 20, from about 12 to about 20, from about 15 to about 20, from about 5 to about 15, from about 8 to about 12, from about 3 to about 5, from about 5 to about 8, or from about 12 to about 15 HEAT repeats) provided that it maintains at least some function of a naturally-occurring IPO3 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). An IPO3 polypeptide fragment can be any appropriate length (e.g., can include any number of amino acids) provided that it maintains at least some function of a naturally- occurring IPO3 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). For example, an IPO3 polypeptide fragment can be from about 100 amino acids in length to about 850 amino acids in length (e.g., from about 100 amino acids to about 800 amino acids, from about 100 amino acids to about 750 amino acids, from about 100 amino acids to about 700 amino acids, from about 100 amino acids to about 650 amino acids, from about 100 amino acids to about 600 amino acids, from about 100 amino acids to about 550 amino acids, from about 100 amino acids to about 500 amino acids, from about 100 amino acids to about 450 amino acids, from about 100 amino acids to about 400 amino acids, from about 100 amino acids to about 350 amino acids, from about 100 amino acids to about 300 amino acids, from about 100 amino acids to about 250 amino acids, from about 100 amino acids to about 200 amino acids, from about 150 amino acids to about 850 amino acids, from about 200 amino acids to about 850 amino acids, from about 250 amino acids to about 850 amino acids, from about 300 amino acids to about 850 amino acids, from about 350 amino acids to about 850 amino acids, from about 400 amino acids to about 850 amino acids, from about 450 amino acids to about 850 amino acids, from about 500 amino acids to about 850 amino acids, from about 550 amino acids to about 850 amino acids, from about 600 amino acids to about 850 amino acids, from about 650 amino Attorney Docket No.07039-2180WO1 / 2022-349 acids to about 850 amino acids, from about 700 amino acids to about 850 amino acids, from about 750 amino acids to about 850 amino acids, from about 200 amino acids to about 800 amino acids, from about 300 amino acids to about 700 amino acids, from about 400 amino acids to about 600 amino acids, from about 200 amino acids to about 400 amino acids, from about 300 amino acids to about 500 amino acids, from about 500 amino acids to about 700 amino acids, or from about 600 amino acids to about 800 amino acids in length) provided that it maintains at least some function of a naturally-occurring IPO3 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). In some cases, an IPO3 polypeptide fragment can comprise, consist essentially of, or consist of an amino acid sequence set forth in Table 3. Table 3. Exemplary IPO3 polypeptide fragments. Truncation Polypeptide Sequence SEQ ID NO: Attorney Docket No.07039-2180WO1 / 2022-349 Attorney Docket No.07039-2180WO1 / 2022-349

Attorney Docket No.07039-2180WO1 / 2022-349 Attorney Docket No.07039-2180WO1 / 2022-349 Attorney Docket No.07039-2180WO1 / 2022-349 Attorney Docket No.07039-2180WO1 / 2022-349 In some cases, an IPO3 polypeptide fragment provided herein can include the amino acid sequence set forth in any one of SEQ ID NOs:26-42 with zero, one, two three, or more (e.g., five, eight, 12, 15, 18, 20, 25, 30, 35, 40, or more) amino acid substitutions (e.g., one or more K?R substitutions) within the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:26-42), with zero, one, two, three, four, or five amino acid residues preceding the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:26-42, and/or with zero, one, two, three, four, or five amino acid residues following the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:26-42), provided that the IPO3 polypeptide fragment provided herein retains at least some activity exhibited by a naturally-occurring IPO3 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). Examples of such IPO3 polypeptide fragments can be those set forth in Table 4. Table 4. Exemplary IPO3 polypeptide fragments. Polypeptide Sequence SEQ ID NO: Attorney Docket No.07039-2180WO1 / 2022-349

Attorney Docket No.07039-2180WO1 / 2022-349 Attorney Docket No.07039-2180WO1 / 2022-349 Attorney Docket No.07039-2180WO1 / 2022-349 p p yp p p yp p , y pp p polypeptide (and/or nucleic acid designed to express an IPO13 polypeptide) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) as described herein. Examples of IPO13 polypeptides and nucleic acids encoding IPO13 polypeptides include, without limitation, those set forth in the NCBI databases at, for example, accession no. NP_055467 (version NP_055467.3), and accession no. NM_014652 (version NM_014652.4), and accession no. NP_666264 (version NP_666264.1). Attorney Docket No.07039-2180WO1 / 2022-349 In some cases, an IPO13 polypeptide can have an amino acid sequence set forth in SEQ ID NO:5 (see, e.g., Example 3). In some cases, a nucleic acid encoding an IPO13 polypeptide can have a nucleotide sequence set forth in SEQ ID NO:6 (see, e.g., Example 3). When a fragment of an importin polypeptide is an IPO13 polypeptide fragment, any appropriate IPO13 polypeptide fragment (and/or nucleic acid designed to express an IPO13 polypeptide fragment) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) as described herein. In some cases, an IPO13 polypeptide fragment can be derived from the amino acid sequence set forth in SEQ ID NO:5. An IPO13 polypeptide fragment can include at least one of the HEAT repeats present in an IPO13 polypeptide (e.g., consecutive or non-consecutive HEAT repeats). For example, an IPO13 polypeptide fragment can include from about 1 HEAT repeat to about 20 HEAT repeats (e.g., from about 1 to about 15, from about 1 to about 12, from about 1 to about 10, from about 1 to about 8, from about 1 to about 5, from about 3 to about 20, from about 5 to about 20, from about 7 to about 20, from about 10 to about 20, from about 12 to about 20, from about 15 to about 20, from about 5 to about 15, from about 8 to about 12, from about 3 to about 5, from about 5 to about 8, or from about 12 to about 15 HEAT repeats) provided that it maintains at least some function of a naturally-occurring IPO13 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). An IPO13 polypeptide fragment can be any appropriate length (e.g., can include any number of amino acids) provided that it maintains at least some function of a naturally- occurring IPO13 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). For example, an IPO13 polypeptide fragment can be from about 100 amino acids in length to about 950 amino acids in length (e.g., from about 100 amino acids to about 800 amino acids, from about 100 amino acids to about 750 amino acids, from about 100 amino acids to about 700 amino acids, from about 100 amino acids to about 650 amino acids, from about 100 amino acids to about 600 amino Attorney Docket No.07039-2180WO1 / 2022-349 acids, from about 100 amino acids to about 550 amino acids, from about 100 amino acids to about 500 amino acids, from about 100 amino acids to about 450 amino acids, from about 100 amino acids to about 400 amino acids, from about 100 amino acids to about 350 amino acids, from about 100 amino acids to about 300 amino acids, from about 100 amino acids to about 250 amino acids, from about 200 amino acids to about 950 amino acids, from about 250 amino acids to about 950 amino acids, from about 300 amino acids to about 950 amino acids, from about 350 amino acids to about 950 amino acids, from about 400 amino acids to about 950 amino acids, from about 450 amino acids to about 950 amino acids, from about 500 amino acids to about 950 amino acids, from about 550 amino acids to about 950 amino acids, from about 600 amino acids to about 950 amino acids, from about 650 amino acids to about 950 amino acids, from about 700 amino acids to about 950 amino acids, from about 750 amino acids to about 950 amino acids, from about 800 amino acids to about 950 amino acids, from about 200 amino acids to about 900 amino acids, from about 300 amino acids to about 800 amino acids, from about 400 amino acids to about 700 amino acids, from about 500 amino acids to about 600 amino acids, from about 200 amino acids to about 400 amino acids, from about 300 amino acids to about 500 amino acids, from about 400 amino acids to about 600 amino acids, from about 500 amino acids to about 700 amino acids, from about 600 amino acids to about 800 amino acids, or from about 700 amino acids to about 900 amino acids in length) provided that it maintains at least some function of a naturally- occurring IPO13 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). In some cases, an IPO13 polypeptide fragment can comprise, consist essentially of, or consist of an amino acid sequence set forth in Table 5. Table 5. Exemplary IPO13 polypeptide fragments. Truncation Polypeptide Sequence SEQ ID NO: Attorney Docket No.07039-2180WO1 / 2022-349 Attorney Docket No.07039-2180WO1 / 2022-349 Attorney Docket No.07039-2180WO1 / 2022-349 Attorney Docket No.07039-2180WO1 / 2022-349

Attorney Docket No.07039-2180WO1 / 2022-349 Attorney Docket No.07039-2180WO1 / 2022-349 In some cases, an IPO13 polypeptide fragment provided herein can include the amino acid sequence set forth in any one of SEQ ID NOs:56-66 with zero, one, two three, or more (e.g., five, eight, 12, 15, 18, 20, 25, 30, 35, 40, or more) amino acid substitutions (e.g., one or more K?R substitutions) within the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:56-66), with zero, one, two, three, four, or five amino acid residues preceding the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:56-66), and/or with zero, one, two, three, four, or five amino acid residues following the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:56-66), provided that the IPO13 polypeptide fragment retains at least some activity exhibited by a naturally-occurring IPO13 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). Examples of such IPO13 polypeptide fragments can be those set forth in Table 6. Table 6. Exemplary IPO13 polypeptide fragments. Polypeptide Sequence SEQ ID NO: MVENVERALHQLYYDPNIENRNLAQRWLMQAQVSPQAWHFSWQLLQPDRVPEIQYF 67 Attorney Docket No.07039-2180WO1 / 2022-349

Attorney Docket No.07039-2180WO1 / 2022-349 Attorney Docket No.07039-2180WO1 / 2022-349 Attorney Docket No.07039-2180WO1 / 2022-349 When an importin polypeptide is an IPO4 polypeptide, any appropriate IPO4 polypeptide (and/or nucleic acid designed to express an IPO4 polypeptide) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) as described herein. Examples of IPO4 polypeptides and nucleic acids encoding IPO4 polypeptides include, without limitation, those set forth in the NCBI databases at, for example, NP_078934 (version NP_078934.3) and accession no. NM_024658 (version NM_024658.4). In some cases, an IPO4 polypeptide can have an amino acid sequence set forth in SEQ ID NO:80 (see, e.g., Example 4). In some cases, a nucleic acid encoding an IPO4 polypeptide can have a nucleotide sequence set forth in SEQ ID NO:81 (see, e.g., Example 4). When a fragment of an importin polypeptide is an IPO4 polypeptide fragment, any appropriate IPO4 polypeptide fragment (and/or nucleic acid designed to express an IPO4 polypeptide fragment) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) as described herein. In some cases, an IPO4 Attorney Docket No.07039-2180WO1 / 2022-349 polypeptide fragment can be derived from the amino acid sequence set forth in SEQ ID NO:80. An IPO4 polypeptide fragment can include at least one of the HEAT repeats present in an IPO4 polypeptide (e.g., consecutive or non-consecutive HEAT repeats). For example, an IPO4 polypeptide fragment can include from about 1 HEAT repeat to about 24 HEAT repeats (e.g., from about 1 to about 20, from about 1 to about 15, from about 1 to about 12, from about 1 to about 10, from about 1 to about 7, from about 1 to about 5, from about 3 to about 24, from about 5 to about 24, from about 8 to about 24, from about 10 to about 24, from about 12 to about 24, from about 15 to about 24, from about 17 to about 24, from about 5 to about 20, from about 8 to about 15, from about 10 to about 12, from about 3 to about 5, from about 5 to about 10, from about 10 to about 15, or from about 15 to about 20 HEAT repeats) provided that it maintains at least some function of a naturally-occurring IPO4 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). An IPO4 polypeptide fragment can be any appropriate length (e.g., can include any number of amino acids) provided that it maintains at least some function of a naturally- occurring IPO4 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). For example, an IPO4 polypeptide fragment can be from about 100 amino acids in length to about 1050 amino acids in length (e.g., from about 100 amino acids to about 1000 amino acids, from about 100 amino acids to about 800 amino acids, from about 100 amino acids to about 600 amino acids, from about 100 amino acids to about 500 amino acids, from about 100 amino acids to about 400 amino acids, from about 100 amino acids to about 300 amino acids, from about 100 amino acids to about 200 amino acids, from about 200 amino acids to about 1050 amino acids, from about 300 amino acids to about 1050 amino acids, from about 500 amino acids to about 1050 amino acids, from about 750 amino acids to about 1050 amino acids, from about 200 amino acids to about 1000 amino acids, from about 300 amino acids to about 900 amino acids, from about 400 amino acids to about 800 amino acids, from about 500 amino acids to about 700 amino acids, Attorney Docket No.07039-2180WO1 / 2022-349 from about 200 amino acids to about 400 amino acids, from about 300 amino acids to about 500 amino acids, from about 400 amino acids to about 600 amino acids, from about 500 amino acids to about 700 amino acids, from about 600 amino acids to about 800 amino acids, from about 700 amino acids to about 900 amino acids, or from about 800 amino acids to about 1000 amino acids in length) provided that it maintains at least some function of a naturally-occurring IPO4 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). In some cases, an IPO4 polypeptide fragment provided herein can include the amino acid sequence set forth in SEQ ID NO:80 with zero, one, two three, or more (e.g., five, eight, 12, 15, 18, 20, 25, 30, 35, 40, or more) amino acid substitutions (e.g., one or more K?R substitutions) within the articulated sequence of the sequence identifier (e.g., SEQ ID NO:80), with zero, one, two, three, four, or five amino acid residues preceding the articulated sequence of the sequence identifier (e.g., SEQ ID NO:80), and/or with zero, one, two, three, four, or five amino acid residues following the articulated sequence of the sequence identifier (e.g., SEQ ID NO:80), provided that the IPO4 polypeptide fragment retains at least some activity exhibited by a naturally-occurring IPO4 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). When an importin polypeptide is an IPO11 polypeptide, any appropriate IPO11 polypeptide (and/or nucleic acid designed to express an IPO11 polypeptide) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) as described herein. Examples of IPO11 polypeptides and nucleic acids encoding IPO4 polypeptides include, without limitation, those set forth in the NCBI databases at, for example, NP_057422 (version NP_057422.3), accession no. NM_016338 (version NM_016338.5), NP_001128251 (version NP_001128251.1and accession no. NM_001134779 (version NM_001134779.2). In some cases, an IPO11 polypeptide can have an amino acid sequence set forth in SEQ ID NO:82 (see, e.g., Example 5). In some cases, a nucleic acid encoding an IPO11 Attorney Docket No.07039-2180WO1 / 2022-349 polypeptide can have a nucleotide sequence set forth in SEQ ID NO:83 (see, e.g., Example 5). When a fragment of an importin polypeptide is an IPO11 polypeptide fragment, any appropriate IPO11 polypeptide fragment (and/or nucleic acid designed to express an IPO11 polypeptide fragment) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) as described herein. In some cases, an IPO11 polypeptide fragment can be derived from the amino acid sequence set forth in SEQ ID NO:82. An IPO11 polypeptide fragment can include at least one of the HEAT repeats present in an IPO11 polypeptide (e.g., consecutive or non-consecutive HEAT repeats). For example, an IPO11 polypeptide fragment can include from about 1 HEAT repeat to about 15 HEAT repeats (e.g., from about 1 to about 12, from about 1 to about 10, from about 1 to about 8, from about 1 to about 5, from about 3 to about 15, from about 5 to about 15, from about 7 to about 15, from about 10 to about 15, from about 12 to about 15, from about 3 to about 12, from about 5 to about 10, from about 3 to about 5, from about 5 to about 7, from about 7 to about 10, or from about 10 to about 12 HEAT repeats) provided that it maintains at least some function of a naturally-occurring IPO11 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). An IPO11 polypeptide fragment can be any appropriate length (e.g., can include any number of amino acids) provided that it maintains at least some function of a naturally- occurring IPO11 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). For example, an IPO11 polypeptide fragment can be from about 100 amino acids in length to about 1000 amino acids in length (e.g., from about 100 amino acids to about 750 amino acids, from about 100 amino acids to about 600 amino acids, from about 100 amino acids to about 500 amino acids, from about 100 amino acids to about 400 amino acids, from about 100 amino acids to about 300 amino acids, from about 100 amino acids to about 200 amino acids, from about 200 amino acids to about 1000 amino acids, from about 300 amino acids to about 1000 amino acids, from about Attorney Docket No.07039-2180WO1 / 2022-349 400 amino acids to about 1000 amino acids, from about 500 amino acids to about 1000 amino acids, from about 600 amino acids to about 1000 amino acids, from about 750 amino acids to about 1000 amino acids, from about 200 amino acids to about 750 amino acids, from about 300 amino acids to about 600 amino acids, from about 400 amino acids to about 500 amino acids, from about 200 amino acids to about 400 amino acids, from about 300 amino acids to about 500 amino acids, from about 400 amino acids to about 600 amino acids, from about 500 amino acids to about 700 amino acids, from about 600 amino acids to about 800 amino acids, or from about 700 amino acids to about 900 amino acids in length) provided that it maintains at least some function of a naturally-occurring IPO11 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). In some cases, an IPO11 polypeptide fragment provided herein can include the amino acid sequence set forth in SEQ ID NO:82 with zero, one, two three, or more (e.g., five, eight, 12, 15, 18, 20, 25, 30, 35, 40, or more) amino acid substitutions (e.g., one or more K?R substitutions) within the articulated sequence of the sequence identifier (e.g., SEQ ID NO:82), with zero, one, two, three, four, or five amino acid residues preceding the articulated sequence of the sequence identifier (e.g., SEQ ID NO:82), and/or with zero, one, two, three, four, or five amino acid residues following the articulated sequence of the sequence identifier (e.g., SEQ ID NO:82), provided that the IPO11 polypeptide fragment retains at least some activity exhibited by a naturally-occurring IPO11 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). When an importin polypeptide is an IPO12 polypeptide, any appropriate IPO12 polypeptide (and/or nucleic acid designed to express an IPO12 polypeptide) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) as described herein. Examples of IPO12 polypeptides and nucleic acids encoding IPO12 polypeptides include, without limitation, those set forth in the NCBI databases at, for example, NP_036602 (version NP_036602.1), accession no. NM_012470 Attorney Docket No.07039-2180WO1 / 2022-349 (version NM_012470.4), accession no. NP_001177957 (version NP_001177957.2), and accession no. NM_001191028 (version NM_001191028.3). In some cases, an IPO12 polypeptide can have an amino acid sequence set forth in SEQ ID NO:84 (see, e.g., Example 6). In some cases, a nucleic acid encoding an IPO12 polypeptide can have a nucleotide sequence set forth in SEQ ID NO:85 (see, e.g., Example 6). When a fragment of an importin polypeptide is an IPO12 polypeptide fragment, any appropriate IPO4 polypeptide fragment (and/or nucleic acid designed to express an IPO12 polypeptide fragment) can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) as described herein. In some cases, an IPO12 polypeptide fragment can be derived from the amino acid sequence set forth in SEQ ID NO:84. An IPO12 polypeptide fragment can include at least one of the HEAT repeats present in an IPO12 polypeptide (e.g., consecutive or non-consecutive HEAT repeats). For example, an IPO12 polypeptide fragment can include from about 1 HEAT repeat to about 20 HEAT repeats (e.g., from about 1 to about 15, from about 1 to about 12, from about 1 to about 10, from about 1 to about 8, from about 1 to about 5, from about 3 to about 20, from about 5 to about 20, from about 7 to about 20, from about 10 to about 20, from about 12 to about 20, from about 15 to about 20, from about 5 to about 15, from about 8 to about 12, from about 3 to about 5, from about 5 to about 8, or from about 12 to about 15 HEAT repeats) provided that it maintains at least some function of a naturally-occurring IPO12 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). An IPO12 polypeptide fragment can be any appropriate length (e.g., can include any number of amino acids) provided that it maintains at least some function of a naturally- occurring IPO12 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). For example, an IPO12 polypeptide fragment can be from about 100 amino acids in length to about 900 amino acids in length Attorney Docket No.07039-2180WO1 / 2022-349 (e.g., from about 100 amino acids to about 750 amino acids, from about 100 amino acids to about 500 amino acids, from about 100 amino acids to about 400 amino acids, from about 100 amino acids to about 300 amino acids, from about 100 amino acids to about 200 amino acids, from about 200 amino acids to about 900 amino acids, from about 300 amino acids to about 900 amino acids, from about 400 amino acids to about 900 amino acids, from about 500 amino acids to about 900 amino acids, from about 750 amino acids to about 900 amino acids, from about 200 amino acids to about 750 amino acids, from about 300 amino acids to about 500 amino acids, from about 200 amino acids to about 400 amino acids, from about 400 amino acids to about 600 amino acids, from about 500 amino acids to about 700 amino acids, or from about 600 amino acids to about 800 amino acids in length) provided that it maintains at least some function of a naturally-occurring IPO12 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). In some cases, an IPO12 polypeptide fragment provided herein can include the amino acid sequence set forth in SEQ ID NO:84 with zero, one, two three, or more (e.g., five, eight, 12, 15, 18, 20, 25, 30, 35, 40, or more) amino acid substitutions (e.g., one or more K?R substitutions) within the articulated sequence of the sequence identifier (e.g., SEQ ID NO:84), with zero, one, two, three, four, or five amino acid residues preceding the articulated sequence of the sequence identifier (e.g., SEQ ID NO:84), and/or with zero, one, two, three, four, or five amino acid residues following the articulated sequence of the sequence identifier (e.g., SEQ ID NO:84), provided that the IPO12 polypeptide fragment retains at least some activity exhibited by a naturally-occurring IPO12 polypeptide (e.g., the ability to reduce at least some tau polypeptide aggregation, to reduce at least some aberrant tau polypeptide hyperphosphorylation, and/or to restore at least some tau polypeptide solubility). Any appropriate method can be used to deliver one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) to a mammal. When one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) are administered to a mammal (e.g., a Attorney Docket No.07039-2180WO1 / 2022-349 human), the one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be administered to the brain of a mammal (e.g., a human). In some cases, one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be administered to the brain of a mammal (e.g., a human) by direct injection into the brain. In some cases, one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be included in (e.g., encapsulated within) a carrier molecule. For example, nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof can be included in (e.g., encapsulated within) a nanoparticle (e.g., a lipid nanoparticle). For example, nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof can be included in an extracellular vesicle. In some cases, one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be administered to the brain of a mammal (e.g., a human) via a carrier molecule that can cross the blood-brain-barrier to enter the brain. Any appropriate method can be used to obtain a karyopherin polypeptide (e.g., a KPNB1 polypeptide) or fragment thereof provided herein (e.g., a polypeptide that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs:7-77). For example, a karyopherin polypeptide (e.g., a KPNB1 polypeptide) or fragment thereof provided herein (e.g., a polypeptide that comprises, consists essentially of, or consists of the amino acid sequence set forth in any one of SEQ ID NOs:7-77) can be obtained by synthesizing the polypeptide of interest using appropriate polypeptide synthesizing techniques such as those described elsewhere (see, e.g., Fields et al., Curr. Protoc. Protein Sci., Chapter 18:Unit 18.1 (2002); Hartrampf et al., Science, 368(6494):980-987 (2020); and Merrifield, J. Am. Chem. Soc., 85:2149–2154 (1963)). Attorney Docket No.07039-2180WO1 / 2022-349 When one or more nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof are administered to a mammal (e.g., a human), the nucleic acid can be in the form of a vector (e.g., a viral vector or a non-viral vector). When nucleic acid encoding a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof is administered to a mammal, the nucleic acid can be used for transient expression of a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof or for stable expression of a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof. In cases where a nucleic acid encoding a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof is used for stable expression of a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof, the nucleic acid encoding a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof can be engineered to integrate into the genome of a cell. Nucleic acid can be engineered to integrate into the genome of a cell using any appropriate method. For example, gene editing techniques (e.g., CRISPR or TALEN gene editing) can be used to integrate nucleic acid designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof into the genome of a cell. When a vector used to deliver nucleic acid encoding a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof to a mammal (e.g., a human) is a viral vector, any appropriate viral vector can be used. A viral vector can be derived from a positive-strand virus or a negative-strand virus. A viral vector can be derived from a virus with a DNA genome or a RNA genome. In some cases, a viral vector can be a chimeric viral vector. In some cases, a viral vector can infect dividing cells. In some cases, a viral vector can infect non-dividing cells. Examples virus-based vectors that can be used to deliver nucleic acid encoding a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof to a mammal (e.g., a human) include, without limitation, virus-based vectors based on adenoviruses, AAVs, Sendai viruses, retroviruses, lentiviruses, herpes simplex viruses (HSV), vaccinia viruses, or baculoviruses. When a vector used to deliver nucleic acid encoding a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof to a mammal (e.g., a human) is a non-viral Attorney Docket No.07039-2180WO1 / 2022-349 vector, any appropriate non-viral vector can be used. In some cases, a non-viral vector can be an expression plasmid (e.g., a cDNA expression vector). In addition to nucleic acid encoding a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof, a vector (e.g., a viral vector or a non-viral vector) can contain one or more regulatory elements operably linked to the nucleic acid encoding a karyopherin polypeptide and/or a fragment thereof. Such regulatory elements can include promoter sequences, enhancer sequences, response elements, signal peptides, internal ribosome entry sequences, polyadenylation signals, terminators, and inducible elements that modulate expression (e.g., transcription or translation) of a nucleic acid. The choice of regulatory element(s) that can be included in a vector depends on several factors, including, without limitation, inducibility, targeting, and the level of expression desired. For example, a promoter can be included in a vector to facilitate transcription of a nucleic acid encoding a karyopherin polypeptide. A promoter can be a naturally occurring promoter or a recombinant promoter. A promoter can be ubiquitous or inducible (e.g., in the presence of tetracycline), and can affect the expression of a nucleic acid encoding a polypeptide in a general or tissue- specific manner (e.g., prion protein (Prp) promoters, synapsin promoters, methyl-CpG- binding protein-2 (MeCP2) promoters, neuron-specific enolase (NSE) promoters, and vesicular glutamate transporter promoter (vGLUT) promoters). Examples of promoters that can be used to drive expression of a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof in cells include, without limitation, Prp promoters, synapsin promoters, MeCP2 promoters, NSE promoters, vGLUT promoters, cytomegalovirus/chicken beta-actin (CBA) hybrid promoters, cytomegalovirus (CMV) early enhancers/promoters, and ubiquitin C (UbC) promoters. As used herein, “operably linked” refers to positioning of a regulatory element in a vector relative to a nucleic acid encoding a polypeptide in such a way as to permit or facilitate expression of the encoded polypeptide. For example, a vector can contain a promoter and nucleic acid encoding a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof. In this case, the promoter is operably linked to a nucleic acid encoding a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof such that it drives expression of the karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof in cells. Attorney Docket No.07039-2180WO1 / 2022-349 In some cases, nucleic acid encoding a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof can contain nucleic acid encoding a label (e.g., a detectable label). For example, a vector can include nucleic acid encoding a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof and nucleic acid encoding a detectable label positioned such that the encoded polypeptide is a fusion polypeptide that includes a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof fused to a detectable polypeptide. In some cases, a detectable label can be a peptide tag. In some cases, a detectable label can be a fluorescent molecule (e.g., a fluorescent polypeptide). Examples of detectable labels that can be used as described herein include, without limitation, an HA tag, a Myc-tag, a FLAG-tag, green fluorescent polypeptides (GFPs; e.g., enhanced GFPs), red fluorescent polypeptides (e.g. mCherry), Halo tags, SNAP-tags, 6xHis-tags, GST-tags, MBP-tags, Strep-tags, and V5-tags. Nucleic acid encoding a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof can be produced by techniques including, without limitation, common molecular cloning, polymerase chain reaction (PCR), chemical nucleic acid synthesis techniques, and combinations of such techniques. For example, PCR or RT-PCR can be used with oligonucleotide primers designed to amplify nucleic acid (e.g., genomic DNA or RNA) encoding a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof. In some cases, one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be formulated into a composition (e.g., a pharmaceutical composition) for administration to a mammal (e.g., a human). For example, one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be formulated into a pharmaceutically acceptable composition for administration to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy). In some cases, one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be formulated together with one or more pharmaceutically acceptable Attorney Docket No.07039-2180WO1 / 2022-349 carriers (additives), excipients, and/or diluents. Examples of pharmaceutically acceptable carriers, excipients, and diluents that can be used in a composition described herein include, without limitation, sucrose, lactose, starch (e.g., starch glycolate), cellulose, cellulose derivatives (e.g., modified celluloses such as microcrystalline cellulose and cellulose ethers like hydroxypropyl cellulose (HPC) and cellulose ether hydroxypropyl methylcellulose (HPMC)), xylitol, sorbitol, mannitol, gelatin, polymers (e.g., polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), crosslinked polyvinylpyrrolidone (crospovidone), carboxymethyl cellulose, polyethylene-polyoxypropylene-block polymers, and crosslinked sodium carboxymethyl cellulose (croscarmellose sodium)), titanium oxide, azo dyes, silica gel, fumed silica, talc, magnesium carbonate, vegetable stearin, magnesium stearate, aluminum stearate, stearic acid, antioxidants (e.g., vitamin A, vitamin E, vitamin C, retinyl palmitate, and selenium), citric acid, sodium citrate, parabens (e.g., methyl paraben and propyl paraben), petrolatum, dimethyl sulfoxide, mineral oil, serum proteins (e.g., human serum albumin), glycine, sorbic acid, potassium sorbate, water, salts or electrolytes (e.g., saline, protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, sodium acetate, and zinc salts), colloidal silica, magnesium trisilicate, polyacrylates, waxes, wool fat, and lecithin. A composition (e.g., a pharmaceutical composition) containing one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be formulated into any appropriate dosage form. Examples of dosage forms include solid or liquid forms including, without limitation, gels, liquids, suspensions, solutions (e.g., sterile solutions), sustained-release formulations, and delayed- release formulations. A composition (e.g., a pharmaceutical composition) containing one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be designed for parenteral (e.g., intracerebral injections, intracerebroventricular (ICV) injections, intra cisterna magna (ICM) injections, intrathecal (IT) injections, intraparenchymal injections, intramuscular injections, and intranasal delivery) Attorney Docket No.07039-2180WO1 / 2022-349 administration. Compositions suitable for parenteral administration include aqueous and non- aqueous sterile injection solutions that can contain anti-oxidants, buffers, bacteriostats, and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents. The formulations can be presented in unit-dose or multi-dose containers, for example, sealed ampules and vials, and may be stored in a freeze dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example water for injections, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules, and tablets. A composition (e.g., a pharmaceutical composition) containing one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be administered locally or systemically. For example, a composition containing one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be administered locally by direct injection (e.g., an intracerebral injection, an intra cisterna magna injection, or an intraventricular injection) to the brain of a mammal (e.g., a human). An effective amount of a composition (e.g., a pharmaceutical composition) containing one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be any amount that can treat the mammal without producing significant toxicity to the mammal. For example, an effective amount of one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof can be from about 0.1 milligrams of polypeptide(s) per kilogram bodyweight of the mammal (mg/kg) to about 100 mg/kg (e.g., from about 0.1 mg/kg to about 75 mg/kg, from about 0.1 mg/kg to about 50 mg/kg, from about 0.1 mg/kg to about 25 mg/kg, from about 0.1 mg/kg to about 15 mg/kg, from about 0.1 mg/kg to about 10 mg/kg, from about 0.1 mg/kg to about 5 mg/kg, from about 0.1 mg/kg to about 1 mg/kg, from about 1 mg/kg to about 100 mg/kg, from about 5 mg/kg to about 100 mg/kg, from about 10 mg/kg to about 100 mg/kg, from Attorney Docket No.07039-2180WO1 / 2022-349 about 25 mg/kg to about 100 mg/kg, from about 50 mg/kg to about 100 mg/kg, from about 75 mg/kg to about 100 mg/kg, from about 1 mg/kg to about 75 mg/kg, from about 5 mg/kg to about 50 mg/kg, from about 10 mg/kg to about 25 mg/kg, from about 1 mg/kg to about 10 mg/kg, from about 5 mg/kg to about 25 mg/kg, from about 10 mg/kg to about 50 mg/kg, or from about 25 mg/kg to about 75 mg/kg). In another example, an effective amount of a viral vector encoding one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof can be from about 1 x 10¹⁰ to about 1 x 10¹⁵ vector genomes per kilogram (vgs/kg) per mammal (e.g., from about 1 x 10¹⁰ to about 1 x 10¹⁵ vgs/kg, from about 1 x 10¹⁰ to about 1 x 10¹⁴ vgs/kg, from about 1 x 10¹⁰ to about 1 x 10¹³ vgs/kg, from about 1 x 10¹⁰ to about 1 x 10¹² vgs/kg, from about 1 x 10¹⁰ to about 1 x 10¹¹ vgs/kg, from about 1 x 10¹¹ to about 1 x 10¹⁵ vgs/kg, from about 1 x 10¹² to about 1 x 10¹⁵ vgs/kg, from about 1 x 10¹³ to about 1 x 10¹⁵ vgs/kg, from about 1 x 10¹⁴ to about 1 x 10¹⁵ vgs/kg, from about 1 x 10¹¹ to about 1 x 10¹⁴ vgs/kg, from about 1 x 10¹² to about 1 x 10¹³ vgs/kg, from about 1 x 10¹¹ to about 1 x 10¹³ vgs/kg, or from about 1 x 10¹² to about 1 x 10¹⁴ vgs/kg, per mammal). The effective amount can remain constant or can be adjusted as a sliding scale or variable dose depending on the mammal’s response to treatment. Various factors can influence the actual effective amount used for a particular application. For example, the frequency of administration, duration of treatment, use of multiple treatment agents, route of administration, and severity of the condition may require an increase or decrease in the actual effective amount administered. The frequency of administration of a composition (e.g., a pharmaceutical composition) containing one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be any frequency that can treat a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) without producing significant toxicity to the mammal. For example, the frequency of administration can be from about two times a day to about once a week, from about twice a day to about twice a week, or from about once a day to about twice a week. The frequency of administration can remain constant or can be variable during the duration of treatment. A course of treatment with a composition containing one or more karyopherin polypeptides Attorney Docket No.07039-2180WO1 / 2022-349 (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) provided herein can include rest periods. As with the effective amount, various factors can influence the actual frequency of administration used for a particular application. For example, the effective amount, duration of treatment, use of multiple treatment agents, route of administration, and severity of the condition may require an increase or decrease in administration frequency. An effective duration for administering a composition (e.g., a pharmaceutical composition) containing one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be any duration that treat a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) without producing significant toxicity to the mammal. For example, the effective duration can vary from several days to several weeks, months, or years. In some cases, the effective duration for the treatment of a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) can range in duration from about one month to about 10 years. Multiple factors can influence the actual effective duration used for a particular treatment. For example, an effective duration can vary with the frequency of administration, effective amount, use of multiple treatment agents, route of administration, and severity of the condition being treated. In some cases, the one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be used as the sole active agent used to treat a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy). In some cases, the methods and materials described herein can include one or more (e.g., one, two, three, four, five or more) additional therapeutic agents used to treat a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) and/or to treat one or more symptoms of a proteinopathy (e.g., a tauopathy). In some cases, a therapeutic agent used to treat a mammal (e.g., a human) having, or at risk of developing, a Attorney Docket No.07039-2180WO1 / 2022-349 proteinopathy (e.g., a tauopathy) can increase progranulin polypeptide levels and/or increased granulin polypeptide levels within the mammal. Examples of therapeutic agents used to treat a proteinopathy (e.g., a tauopathy) and/or symptoms of a proteinopathy (e.g., a tauopathy) that can be administered to a mammal (e.g., a human) having, or at risk of developing, a proteinopathy (e.g., a tauopathy) together with one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) include, without limitation, AL001 (also referred to as latozinemab), AL002, AADvac1, ACI-3024, ACI-35, APNmAb005, ASN51, ASN90, AZP2006, Anle138b, BIIB080, bepranemab, dasatinib, quercetin, E2814, JNJ-63733657, LMTM, LY3372689, Lu AF87908, PNT001, semorinemab, TPI 287, zagotenemab, cholinesterase inhibitors, N- methyl-D-aspartate (NMDA) receptor antagonists, selective serotonin reuptake inhibitors, and any combinations thereof. In some cases, the one or more additional therapeutic agents can be administered together with one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof); e.g., in the same composition). In some cases, the one or more additional therapeutic agents can be administered independent of the one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof). When the one or more additional therapeutic agents are administered independent of the one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof), the one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof) can be administered first, and the one or more additional therapeutic agents administered second, or vice versa. In some cases, the methods and materials described herein can include subjecting a mammal having, or at risk of developing, a proteinopathy (e.g., a tauopathy) to one or more Attorney Docket No.07039-2180WO1 / 2022-349 (e.g., one, two, three, four, five or more) additional treatments (e.g., therapeutic interventions) that are effective to treat a proteinopathy (e.g., a tauopathy) and/or to treat one or more symptoms of a proteinopathy (e.g., a tauopathy). Examples of therapies that can be used to treat a proteinopathy (e.g., a tauopathy) and/or symptoms of a proteinopathy include, without limitation, physical therapy, occupational therapy, speech therapy, and any combinations thereof. In some cases, the one or more additional treatments that are effective to treat a proteinopathy (e.g., a tauopathy) can be performed at the same time as the administration of the one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof). In some cases, the one or more additional treatments that are effective to treat a proteinopathy (e.g., a tauopathy) can be performed before and/or after the administration of the one or more karyopherin polypeptides (e.g., a KPNB1 polypeptide) and/or fragments thereof (and/or nucleic acids designed to express a karyopherin polypeptide (e.g., a KPNB1 polypeptide) and/or a fragment thereof). The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims. EXAMPLES Example 1: Exemplary Karyopherin Sequences Amino acid sequence of an exemplary KPNB1 polypeptide MELITILEKTVSPDRLELEAAQKFLERAAVENLPTFLVELSRVLANPGNSQVARVAAGLQIK NSLTSKDPDIKAQYQQRWLAIDANARREVKNYVLQTLGTETYRPSSASQCVAGIACAEIPVN QWPELIPQLVANVTNPNSTEHMKESTLEAIGYICQDIDPEQLQDKSNEILTAIIQGMRKEEP SNNVKLAATNALLNSLEFTKANFDKESERHFIMQVVCEATQCPDTRVRVAALQNLVKIMSLY YQYMETYMGPALFAITIEAMKSDIDEVALQGIEFWSNVCDEEMDLAIEASEAAEQGRPPEHT SKFYAKGALQYLVPILTQTLTKQDENDDDDDWNPCKAAGVCLMLLATCCEDDIVPHVLPFIK EHIKNPDWRYRDAAVMAFGCILEGPEPSQLKPLVIQAMPTLIELMKDPSVVVRDTAAWTVGR ICELLPEAAINDVYLAPLLQCLIEGLSAEPRVASNVCWAFSSLAEAAYEAADVADDQEEPAT YCLSSSFELIVQKLLETTDRPDGHQNNLRSSAYESLMEIVKNSAKDCYPAVQKTTLVIMERL QQVLQMESHIQSTSDRIQFNDLQSLLCATLQNVLRKVQHQDALQISDVVMASLLRMFQSTAG SGGVQEDALMAVSTLVEVLGGEFLKYMEAFKPFLGIGLKNYAEYQVCLAAVGLVGDLCRALQ Attorney Docket No.07039-2180WO1 / 2022-349 SNIIPFCDEVMQLLLENLGNENVHRSVKPQILSVFGDIALAIGGEFKKYLEVVLNTLQQASQ AQVDKSDYDMVDYLNELRESCLEAYTGIVQGLKGDQENVHPDVMLVQPRVEFILSFIDHIAG DEDHTDGVVACAAGLIGDLCTAFGKDVLKLVEARPMIHELLTEGRRSKTNKAKTLATWATKE LRKLKNQA (SEQ ID NO:1) Nucleotide sequence of a nucleic acid encoding an exemplary KPNB1 polypeptide ATGGAGCTGATCACCATTCTCGAGAAGACCGTGTCTCCCGATCGGCTGGAGCTGGAAGCGGC GCAGAAGTTCCTGGAGCGTGCGGCCGTGGAGAACCTGCCCACTTTCCTTGTGGAACTGTCCA GAGTGCTGGCAAATCCAGGAAACAGTCAGGTTGCCAGAGTTGCAGCTGGTCTACAAATCAAG AACTCTTTGACATCTAAAGATCCAGATATCAAGGCACAATATCAGCAGAGGTGGCTTGCTAT TGATGCTAATGCTCGACGAGAAGTCAAGAACTATGTTTTGCAGACATTGGGTACAGAAACTT ACCGGCCTAGTTCTGCCTCACAGTGTGTGGCTGGTATTGCTTGTGCAGAGATCCCAGTAAAC CAGTGGCCAGAACTCATTCCTCAGCTGGTGGCCAATGTCACAAACCCCAACAGCACAGAGCA CATGAAGGAGTCGACATTGGAAGCCATCGGTTATATTTGCCAAGATATAGACCCAGAGCAGC TACAAGATAAATCCAATGAGATTCTGACTGCCATAATCCAGGGGATGAGGAAAGAAGAGCCT AGTAATAATGTGAAGCTAGCTGCTACGAATGCACTCCTGAACTCATTGGAGTTCACCAAAGC AAACTTTGATAAAGAGTCTGAAAGGCACTTTATTATGCAGGTGGTCTGTGAAGCCACACAGT GTCCAGATACGAGGGTACGAGTGGCTGCTTTACAGAATCTGGTGAAGATAATGTCCTTATAT TATCAGTACATGGAGACATATATGGGTCCTGCTCTTTTTGCAATCACAATCGAAGCAATGAA AAGTGACATTGATGAGGTGGCTTTACAAGGGATAGAATTCTGGTCCAATGTCTGTGATGAGG AAATGGATTTGGCCATTGAAGCTTCAGAGGCAGCAGAACAAGGACGGCCCCCTGAGCACACC AGCAAGTTTTATGCGAAGGGAGCACTACAGTATCTGGTTCCAATCCTCACACAGACACTAAC TAAACAGGACGAAAATGATGATGACGATGACTGGAACCCCTGCAAAGCAGCAGGGGTGTGCC TCATGCTTCTGGCCACCTGCTGTGAAGATGACATTGTCCCACATGTCCTCCCCTTCATTAAA GAACACATCAAGAACCCAGATTGGCGGTACCGGGATGCAGCAGTGATGGCTTTTGGTTGTAT CTTGGAAGGACCAGAGCCCAGTCAGCTCAAACCACTAGTTATACAGGCTATGCCCACCCTAA TAGAATTAATGAAAGACCCCAGTGTAGTTGTTCGAGATACAGCTGCATGGACTGTAGGCAGA ATTTGTGAGCTGCTTCCTGAAGCTGCCATCAATGATGTCTACTTGGCTCCCCTGCTACAGTG TCTGATTGAGGGTCTCAGTGCTGAACCCAGAGTGGCTTCAAATGTGTGCTGGGCTTTCTCCA GTCTGGCTGAAGCTGCTTATGAAGCTGCAGACGTTGCTGATGATCAGGAAGAACCAGCTACT TACTGCTTATCTTCTTCATTTGAACTCATAGTTCAGAAGCTCCTAGAGACTACAGACAGACC TGATGGACACCAGAACAACCTGAGGAGTTCTGCATATGAATCTCTGATGGAAATTGTGAAAA ACAGTGCCAAGGATTGTTATCCTGCTGTCCAGAAAACGACTTTGGTCATCATGGAACGACTG CAACAGGTTCTTCAGATGGAGTCACATATCCAGAGCACATCCGATAGAATCCAGTTCAATGA CCTTCAGTCTTTACTCTGTGCAACTCTTCAGAATGTTCTTCGGAAAGTGCAACATCAAGATG CTTTGCAGATCTCTGATGTGGTTATGGCCTCCCTGTTAAGGATGTTCCAAAGCACAGCTGGG TCTGGGGGAGTACAAGAGGATGCCCTGATGGCAGTTAGCACACTGGTGGAAGTGTTGGGTGG TGAATTCCTCAAGTACATGGAGGCCTTTAAACCCTTCCTGGGCATTGGATTAAAAAATTATG Attorney Docket No.07039-2180WO1 / 2022-349 CTGAATACCAGGTTTGTTTGGCAGCTGTGGGCTTAGTGGGAGACTTGTGCCGTGCCCTGCAA TCCAACATCATACCTTTCTGTGACGAGGTGATGCAGCTGCTTCTGGAAAATTTGGGGAATGA GAACGTCCACAGGTCTGTGAAGCCGCAGATTCTGTCAGTGTTTGGTGATATTGCCCTTGCTA TTGGAGGAGAGTTTAAAAAATACTTAGAGGTTGTATTGAATACTCTTCAGCAGGCCTCCCAA GCCCAGGTGGACAAGTCAGACTATGACATGGTGGATTATCTGAATGAGCTAAGGGAAAGCTG CTTGGAAGCCTATACTGGAATCGTCCAGGGATTAAAGGGGGATCAGGAGAACGTACACCCGG ATGTGATGCTGGTACAACCCAGAGTAGAATTTATTCTGTCTTTCATTGACCACATTGCTGGA GATGAGGATCACACAGATGGAGTAGTAGCTTGTGCTGCTGGACTAATAGGGGACTTATGTAC AGCATTTGGGAAGGATGTACTGAAATTAGTAGAAGCTAGGCCAATGATCCATGAATTGTTAA CTGAAGGGCGGAGATCGAAGACTAACAAAGCAAAAACCCTTGCTACATGGGCAACAAAAGAA CTGAGGAAACTGAAGAACCAAGCTTAA (SEQ ID NO:2) Example 2: Exemplary IPO3 Sequences Amino acid sequence of an exemplary IPO3A polypeptide MDWQPDEQGLQQVLQLLKDSQSPNTATQRIVQDKLKQLNQFPDFNNYLIFVLTRLKSEDEPT RSLSGLILKNNVKAHYQSFPPPVADFIKQECLNNIGDASSLIRATIGILITTIASKGELQMW PELLPQLCNLLNSEDYNTCEGAFGALQKICEDSSELLDSDALNRPLNIMIPKFLQFFKHCSP KIRSHAIACVNQFIMDRAQALMDNIDTFIEHLFALAVDDDPEVRKNVCRALVMLLEVRIDRL IPHMHSIIQYMLQRTQDHDENVALEACEFWLTLAEQPICKEVLASHLVQLIPILVNGMKYSE IDIILLKGDVEEDEAVPDSEQDIKPRFHKSRTVTLPHEAERPDGSEDAEDDDDDDALSDWNL RKCSAAALDVLANVFREELLPHLLPLLKGLLFHPEWVVKESGILVLGAIAEGCMQGMVPYLP ELIPHLIQCLSDKKALVRSIACWTLSRYAHWVVSQPPDMHLKPLMTELLKRILDGNKRVQEA ACSAFATLEEEACTELVPYLSYILDTLVFAFGKYQHKNLLILYDAIGTLADSVGHHLNQPEY IQKLMPPLIQKWNELKDEDKDLFPLLECLSSVATALQSGFLPYCEPVYQRCVTLVQKTLAQA MMYTQHPEQYEAPDKDFMIVALDLLSGLAEGLGGHVEQLVARSNIMTLLFQCMQDSMPEVRQ SSFALLGDLTKACFIHVKPCIAEFMPILGTNLNPEFISVCNNATWAIGEICMQMGAEMQPYV QMVLNNLVEIINRPNTPKTLLENTAITIGRLGYVCPQEVAPMLQQFIRPWCTSLRNIRDNEE KDSAFRGICMMIGVNPGGVVQDFIFFCDAVASWVSPKDDLRDMFYKILHGFKDQVGEDNWQQ FSEQFPPLLKERLAAFYGV (SEQ ID NO:3) Nucleotide sequence of a nucleic acid encoding an exemplary IPO3A polypeptide ATGGACTGGCAGCCAGACGAGCAGGGCCTGCAGCAGGTCCTGCAGCTGCTCAAAGACTCACA GTCGCCCAACACAGCCACTCAGCGCATCGTGCAGGATAAACTCAAACAACTCAATCAGTTTC CTGACTTCAACAACTACCTGATTTTCGTCCTGACCAGACTCAAGTCAGAAGATGAGCCAACG CGCTCTCTCAGTGGCCTCATCCTCAAGAACAACGTGAAGGCACACTATCAGAGCTTCCCACC Attorney Docket No.07039-2180WO1 / 2022-349 CCCTGTGGCAGACTTCATCAAACAGGAGTGTCTCAACAACATTGGCGATGCCTCCTCGCTCA TCCGAGCCACCATTGGCATTCTCATCACCACCATCGCTTCCAAGGGTGAGCTGCAGATGTGG CCCGAGCTGCTGCCCCAGCTCTGCAACCTGCTTAACTCGGAGGATTACAACACTTGTGAGGG AGCCTTTGGAGCCCTGCAGAAGATCTGTGAAGACTCATCAGAGCTTCTGGACAGTGACGCCC TCAACAGGCCCCTCAACATCATGATCCCCAAGTTCCTGCAGTTCTTCAAGCACTGCAGTCCC AAGATCCGGTCCCACGCCATCGCCTGCGTGAACCAGTTCATCATGGACCGGGCCCAGGCGCT GATGGACAATATTGACACCTTCATCGAGCACCTATTTGCCCTGGCTGTGGATGATGACCCCG AGGTGCGGAAGAATGTGTGCCGTGCCCTGGTGATGCTTCTGGAAGTGCGGATTGACAGGCTC ATCCCCCACATGCACAGCATCATCCAGTACATGCTGCAGAGGACCCAGGACCATGATGAGAA CGTTGCCCTTGAGGCCTGTGAGTTCTGGCTGACGCTGGCCGAGCAGCCCATCTGCAAGGAAG TCCTGGCCTCCCATCTGGTCCAGTTGATCCCCATCTTGGTGAATGGGATGAAGTACTCGGAA ATTGACATCATCCTGCTCAAGGGGGATGTGGAGGAGGATGAGGCTGTCCCCGACAGTGAGCA GGACATCAAGCCACGCTTCCACAAGTCACGCACGGTCACACTGCCCCACGAGGCTGAGCGGC CTGATGGCTCCGAGGACGCGGAGGATGACGATGATGATGATGCTCTGTCCGACTGGAATTTG AGGAAGTGCTCAGCGGCTGCACTGGACGTCCTCGCCAATGTCTTCCGGGAGGAACTGCTGCC CCACCTACTCCCACTACTCAAAGGCCTCCTCTTCCACCCCGAGTGGGTGGTCAAGGAGTCGG GCATCCTGGTGCTGGGCGCCATTGCTGAGGGCTGCATGCAGGGCATGGTGCCCTACCTGCCT GAGCTGATCCCGCACCTGATCCAGTGCCTGTCGGATAAGAAGGCCTTGGTCCGCTCCATCGC CTGCTGGACGCTGAGCCGCTATGCCCACTGGGTGGTCAGCCAGCCACCCGACATGCACCTCA AGCCCCTGATGACAGAGCTGCTCAAACGCATCCTGGATGGCAACAAGAGGGTACAGGAGGCG GCCTGCAGTGCTTTTGCCACCCTGGAGGAAGAGGCCTGCACGGAGCTGGTGCCCTACCTCAG CTACATCCTGGACACCCTTGTCTTTGCCTTTGGGAAATACCAGCACAAGAACCTGCTCATCC TCTATGACGCCATTGGCACCCTGGCCGACTCTGTAGGCCACCACCTCAACCAGCCGGAATAC ATCCAGAAGCTGATGCCCCCACTGATCCAGAAGTGGAATGAGCTCAAGGACGAAGACAAGGA CCTCTTCCCCCTGCTGGAGTGTCTGTCATCGGTGGCCACCGCCCTGCAGAGTGGCTTCCTGC CTTACTGTGAGCCCGTCTACCAGCGCTGTGTCACCCTGGTGCAGAAGACACTGGCTCAGGCC ATGATGTACACCCAGCACCCTGAGCAGTATGAGGCTCCCGACAAGGACTTCATGATCGTAGC ACTGGATCTGCTCAGCGGCCTGGCCGAGGGCCTGGGTGGTCACGTGGAGCAGCTGGTGGCCC GCAGCAACATCATGACATTGCTGTTCCAGTGCATGCAGGACTCGATGCCTGAGGTCCGGCAG AGCTCCTTTGCCCTCCTGGGAGACCTCACCAAAGCCTGCTTCATCCATGTCAAGCCCTGTAT CGCCGAGTTCATGCCCATTCTGGGCACCAACCTGAACCCAGAGTTCATCTCCGTCTGCAACA ACGCCACCTGGGCCATTGGTGAAATCTGCATGCAGATGGGGGCAGAGATGCAGCCTTATGTG CAGATGGTCCTCAACAACCTGGTGGAAATCATTAACCGACCCAACACACCCAAGACACTGCT GGAAAACACAGCCATCACCATCGGCCGCTTGGGCTACGTGTGCCCCCAGGAGGTGGCACCCA TGCTGCAGCAGTTCATCCGGCCTTGGTGCACGTCCCTCAGGAACATCAGGGACAACGAGGAG AAGGACTCAGCCTTCCGCGGCATCTGCATGATGATCGGTGTCAACCCGGGGGGCGTTGTGCA GGACTTTATTTTCTTCTGCGATGCTGTAGCCTCCTGGGTGAGCCCGAAGGATGACCTTCGGG ACATGTTTTATAAGATTCTCCACGGCTTCAAAGACCAAGTTGGGGAAGATAACTGGCAGCAG TTCTCTGAGCAATTCCCGCCGCTGCTCAAGGAGAGGCTGGCGGCTTTCTATGGGGTCTAG Attorney Docket No.07039-2180WO1 / 2022-349 (SEQ ID NO:4) Amino acid sequence of an exemplary IPO3B polypeptide MDWQPDEQGLQQVLQLLKDSQSPNTATQRIVQDKLKQLNQFPDFNNYLIFVLTRLKSEDEPT RSLSGLILKNNVKAHYQSFPPPVADFIKQECLNNIGDASSLIRATIGILITTTASKGELQMW PELLPQLCNLLNSEDYNTCGGAFGALQKICEDSSELLDSDAPNRPLNIMIPKFLQFFKHCSP KIRSHAIACVNQFIMDRAQALMDNIDTFIEHLFALAVDDDPEVRKNVCRALVMLLEVRIDRL IPHMHSIIQYMLQRTQDHDENVALEACEFWLTLAEQPICKEVLASHLVQLIPILVNGMKYSE IDIILLKGDVEEDEAVPDSEQDIKPRFHKSRTVTLPHEAERPDGSEDAEDDDDDDALSDWNL RKCSAAALDVLANVFREELLPHLLPLLKGLLFHPEWVVKESGILVLGAIAEGCMQGMVPYLP ELIPHLIQCLSDKKALVRSIACWTLSRYAHWVVSQPPDMHLKPLMTELLKRILDGNKRVQEA ACSAFATLEEEACTELVSYLSYILDTLVFAFGKYQHKNLLILYDAIGTLADSVGHHLNQPEY IQKLMPPLIQKWNELRDEDKDLFPLLECLSSVATALQSGFLPYCEPVYQRCVTLVQKTLAQA MMYTQHPEQYEAPDKDFMIVALDLLSGLAEGLGGHVEQLVARSNIMTLLFQCMQDSMPEVRQ SSFALLGDLTKACFIHVKPCIAEFMPILGTNLNPEFISVCNNATWAIGEICMQMGAEMQPYV QMVLNNLVEIINRPNTPKTLLENTGRLTSPSAIPAITIGRLGYVCPQEVAPMLQQFIRPWCT SLRNIRDNEEKDSAFRGICMMIGVNPGGVVQDFIFFCDAVASWVSPKDDLRDMFYKILHGFK DQVGEDNWQQFSEQFPPLLKERLAAFYGV (SEQ ID NO:78) Nucleotide sequence of a nucleic acid encoding an exemplary IPO3B polypeptide ATGGACTGGCAGCCAGACGAGCAGGGCCTGCAGCAGGTCCTGCAGCTGCTCAAAGACTCACA GTCGCCCAACACAGCCACTCAGCGCATCGTGCAGGATAAACTCAAACAACTCAATCAGTTTC CTGACTTCAACAACTACCTGATTTTCGTCCTGACCAGACTCAAGTCAGAAGATGAGCCAACG CGCTCTCTCAGTGGCCTCATCCTCAAGAACAACGTGAAGGCACACTATCAGAGCTTCCCACC CCCTGTGGCAGACTTCATCAAACAGGAGTGTCTCAACAACATTGGCGATGCCTCCTCGCTCA TCCGAGCCACCATTGGCATTCTCATCACCACCACCGCTTCCAAGGGTGAGCTGCAGATGTGG CCCGAGCTGCTGCCCCAGCTCTGCAACCTGCTTAACTCGGAGGATTACAACACTTGTGGGGG AGCCTTTGGAGCCCTGCAGAAGATCTGTGAAGACTCATCAGAGCTTCTGGACAGTGACGCCC CCAACAGGCCCCTCAACATCATGATCCCCAAGTTCCTGCAGTTCTTCAAGCACTGCAGTCCC AAGATCCGGTCCCACGCCATCGCCTGCGTGAACCAGTTCATCATGGACCGGGCCCAGGCGCT GATGGACAATATTGACACCTTCATCGAGCACCTATTTGCCCTGGCTGTGGATGATGACCCCG AGGTGCGGAAGAATGTGTGCCGTGCCCTGGTGATGCTTCTGGAAGTGCGGATTGACAGGCTC ATCCCCCACATGCACAGCATCATCCAGTACATGCTGCAGAGGACCCAGGACCATGATGAGAA CGTTGCCCTTGAGGCCTGTGAGTTCTGGCTGACGCTGGCCGAGCAGCCCATCTGCAAGGAAG TCCTGGCCTCCCATCTGGTCCAGTTGATCCCCATCTTGGTGAATGGGATGAAGTACTCGGAA ATTGACATCATCCTGCTCAAGGGGGATGTGGAGGAGGATGAGGCTGTCCCCGACAGTGAGCA GGACATCAAGCCACGCTTCCACAAGTCACGCACGGTCACACTGCCCCACGAGGCTGAGCGGC Attorney Docket No.07039-2180WO1 / 2022-349 CTGATGGCTCCGAGGACGCGGAGGATGACGATGATGATGATGCTCTGTCCGACTGGAATTTG AGGAAGTGCTCAGCGGCTGCACTGGACGTCCTCGCCAATGTCTTCCGGGAGGAACTGCTGCC CCACCTACTCCCACTACTCAAAGGCCTCCTCTTCCACCCCGAGTGGGTGGTCAAGGAGTCGG GCATCCTGGTGCTGGGCGCCATTGCTGAGGGCTGCATGCAGGGCATGGTGCCCTACCTGCCT GAGCTGATCCCGCACCTGATCCAGTGCCTGTCGGATAAGAAGGCCTTGGTCCGCTCCATCGC CTGCTGGACGCTGAGCCGCTATGCCCACTGGGTGGTCAGCCAGCCACCCGACATGCACCTCA AGCCCCTGATGACAGAGCTGCTCAAACGCATCCTGGATGGCAACAAGAGGGTACAGGAGGCG GCCTGCAGTGCTTTTGCCACCCTGGAGGAAGAGGCCTGTACGGAGCTGGTGTCCTACCTCAG CTACATCCTGGACACCCTTGTCTTTGCCTTTGGGAAATACCAGCACAAGAACCTGCTCATCC TCTATGACGCCATTGGCACCCTGGCCGACTCTGTAGGCCACCACCTCAACCAGCCGGAATAC ATCCAGAAGCTGATGCCCCCACTGATCCAGAAGTGGAATGAGCTCAGGGACGAAGACAAGGA CCTCTTCCCCCTGCTGGAGTGTCTGTCATCGGTGGCCACCGCCCTGCAGAGTGGCTTCCTGC CTTACTGTGAGCCCGTCTACCAGCGCTGTGTCACCCTGGTGCAGAAGACACTGGCTCAGGCC ATGATGTACACCCAGCACCCTGAGCAGTATGAGGCTCCCGACAAGGACTTCATGATCGTAGC ACTGGATCTGCTCAGCGGCCTGGCCGAGGGCCTGGGTGGTCACGTGGAGCAGCTGGTGGCCC GCAGCAACATCATGACATTGCTGTTCCAGTGCATGCAGGACTCGATGCCTGAGGTCCGGCAG AGCTCCTTTGCCCTCCTGGGAGACCTCACCAAAGCCTGCTTCATCCATGTCAAGCCCTGTAT CGCCGAGTTCATGCCCATTCTGGGCACCAACCTGAACCCAGAGTTCATCTCCGTCTGCAACA ACGCCACCTGGGCCATTGGTGAAATCTGCATGCAGATGGGGGCAGAGATGCAGCCTTATGTG CAGATGGTCCTCAACAACCTGGTGGAAATCATTAACCGACCCAACACACCCAAGACACTGCT GGAAAACACAGGTCGCCTGACGAGTCCCTCTGCCATTCCAGCCATCACCATCGGCCGCTTGG GCTACGTGTGCCCCCAGGAGGTGGCACCCATGCTGCAGCAGTTCATCCGGCCTTGGTGCACG TCCCTCAGGAACATCAGGGACAACGAGGAGAAGGACTCAGCCTTCCGCGGCATCTGCATGAT GATCGGTGTCAACCCGGGGGGCGTTGTGCAGGACTTTATTTTCTTCTGCGATGCTGTAGCCT CCTGGGTGAGCCCGAAGGATGACCTTCGGGACATGTTTTATAAGATTCTCCACGGCTTCAAA GACCAAGTTGGGGAAGATAACTGGCAGCAGTTCTCTGAGCAATTCCCGCCGCTGCTCAAGGA GAGGCTGGCGGCTTTCTATGGGGTCTAG (SEQ ID NO:79) Example 3: Exemplary IPO13 Sequences Amino acid sequence of an exemplary IPO13 polypeptide MERREEQPGAAGAGAAPALDFTVENVEKALHQLYYDPNIENKNLAQKWLMQAQVSPQAWHFS WQLLQPDKVPEIQYFGASALHIKISRYWSDIPTDQYESLKAQLFTQITRFASGSKIVLTRLC VALASLALSMMPDAWPCAVADMVRLFQAEDSPVDGQGRCLALLELLTVLPEEFQTSRLPQYR KGLVRTSLAVECGAVFPLLEQLLQQPSSPSCVRQKVLKCFSSWVQLEVPLQDCEALIQAAFA ALQDSELFDSSVEAIVNAISQPDAQRYVNTLLKLIPLVLGLQEQLRQAVQNGDMETSHGICR IAVALGENHSRALLDQVEHWQSFLALVNMIMFCTGIPGHYPVNETTSSLTLTFWYTLQDDIL SFEAEKQAVYQQVYRPVYFQLVDVLLHKAQFPSDEEYGFWSSDEKEQFRIYRVDISDTLMYV Attorney Docket No.07039-2180WO1 / 2022-349 YEMLGAELLSNLYDKLGRLLTSSEEPYSWQHTEALLYGFQSIAETIDVNYSDVVPGLIGLIP RISISNVQLADTVMFTIGALSEWLADHPVMINSVLPLVLHALGNPELSVSSVSTLKKICREC KYDLPPYAANIVAVSQDVLMKQIHKTSQCMWLMQALGFLLSALQVEEILKNLHSLISPYIQQ LEKLAEEIPNPSNKLAIVHILGLLSNLFTTLDISHHEDDHEGPELRKLPVPQGPNPVVVVLQ QVFQLIQKVLSKWLNDAQVVEAVCAIFEKSVKTLLDDFAPMVPQLCEMLGRMYSTIPQASAL DLTRQLVHIFAHEPAHFPPIEALFLLVTSVTLTLFQQGPRDHPDIVDSFMQLLAQALKRKPD LFLCERLDVKSVFQCAVLALKFPEAPTVKASCGFFTELLPRCGEVESVGKVVQEDGRMLLIA VLEAIGGQASRSLMDCFADILFALNKHCFSLLSMWIKEALQPPGFPSARLSPEQKDTFSQQI LRERVNKRRVKEMVKEFTLLCRGLHGTDYTADY (SEQ ID NO:5) Nucleotide sequence of a nucleic acid encoding an exemplary IPO13 polypeptide ATGGAGCGGCGGGAGGAGCAGCCGGGGGCTGCAGGGGCTGGAGCAGCACCAGCCTTGGACTT CACTGTGGAGAACGTGGAGAAGGCGCTGCACCAGCTCTACTATGATCCCAACATTGAGAATA AGAACCTGGCTCAGAAGTGGCTGATGCAGGCCCAGGTCTCCCCACAGGCCTGGCACTTCAGC TGGCAGCTACTGCAGCCCGACAAGGTACCAGAGATCCAGTACTTTGGGGCCAGTGCTCTTCA CATCAAGATCTCTCGCTACTGGAGTGACATCCCCACTGACCAGTATGAAAGCCTAAAGGCAC AGCTCTTCACCCAGATCACCCGCTTTGCCAGTGGCTCCAAGATTGTACTGACTCGGCTGTGC GTGGCACTGGCCTCACTGGCTCTCAGCATGATGCCTGATGCTTGGCCATGTGCTGTGGCAGA TATGGTACGACTCTTCCAGGCTGAGGACTCACCAGTGGATGGGCAGGGCCGCTGCCTAGCCC TGTTAGAGCTGCTGACAGTGCTGCCTGAGGAGTTCCAGACCAGTCGCCTACCCCAGTACCGC AAAGGCCTGGTGCGGACCAGCCTGGCGGTGGAATGTGGGGCTGTCTTCCCGCTGCTGGAGCA GCTGCTACAGCAGCCCAGCTCACCCAGCTGTGTGCGTCAGAAGGTGCTCAAGTGTTTCTCCA GCTGGGTGCAGCTGGAGGTGCCGCTGCAGGACTGTGAGGCGCTCATTCAGGCTGCCTTTGCT GCTCTGCAGGACTCGGAGCTCTTCGACAGCAGTGTGGAGGCCATTGTGAATGCCATCTCACA GCCTGATGCCCAGAGGTACGTGAACACACTCCTGAAACTCATCCCGCTGGTGCTGGGTCTGC AGGAACAACTGCGGCAGGCAGTGCAGAATGGGGACATGGAGACCTCCCATGGCATCTGTCGC ATCGCTGTGGCCCTGGGCGAGAACCACTCCCGGGCCTTGCTGGACCAAGTAGAGCACTGGCA GAGTTTCCTGGCACTCGTCAACATGATTATGTTCTGCACAGGCATCCCTGGCCACTATCCTG TCAATGAGACCACCAGCTCCCTAACCCTCACCTTCTGGTACACACTGCAGGATGATATTCTA TCCTTTGAGGCAGAGAAGCAGGCTGTATACCAGCAGGTGTACCGGCCAGTCTACTTCCAGCT GGTGGATGTGCTTCTGCACAAGGCCCAGTTCCCTTCTGATGAGGAATATGGATTCTGGTCCT CAGACGAGAAGGAGCAGTTCCGAATTTACAGGGTGGACATCTCAGACACGCTCATGTATGTC TATGAGATGTTGGGGGCCGAGCTGCTCAGCAACCTCTATGACAAGCTGGGTCGTTTGCTCAC CAGCTCAGAGGAGCCCTACTCCTGGCAGCACACAGAGGCCCTCCTCTACGGCTTCCAATCCA TCGCAGAGACCATTGACGTCAACTATTCTGATGTGGTGCCTGGGCTCATTGGCCTCATCCCA CGGATCAGCATCAGCAACGTGCAGCTGGCAGACACTGTCATGTTCACCATTGGAGCTCTGTC TGAATGGCTGGCTGACCACCCCGTCATGATCAACAGTGTTCTGCCCTTGGTACTGCATGCCC TAGGCAATCCTGAGCTGTCTGTCTCTTCTGTGTCCACCCTCAAGAAGATCTGCCGAGAGTGC Attorney Docket No.07039-2180WO1 / 2022-349 AAGTATGACCTGCCTCCCTATGCTGCCAACATTGTGGCTGTGTCCCAGGATGTGCTGATGAA ACAGATCCACAAGACAAGCCAGTGCATGTGGCTGATGCAGGCGCTGGGCTTCCTGCTGTCAG CTCTTCAAGTGGAGGAGATCCTTAAGAACCTGCACTCGCTTATCTCACCCTATATCCAGCAA CTGGAGAAGCTGGCAGAGGAGATACCCAATCCCTCCAACAAGCTGGCCATTGTTCACATCTT GGGGCTTCTCTCCAACCTCTTCACCACACTGGACATCAGTCATCATGAGGATGATCATGAAG GCCCTGAGCTTCGGAAGCTGCCAGTGCCACAGGGACCCAACCCCGTGGTGGTGGTGCTGCAG CAGGTCTTCCAGCTTATCCAGAAGGTGCTGAGCAAATGGTTGAATGATGCCCAGGTTGTGGA GGCGGTGTGCGCTATCTTTGAGAAGTCTGTTAAGACGCTGCTGGATGACTTTGCCCCCATGG TGCCACAGCTGTGTGAGATGCTGGGTCGGATGTACAGCACCATCCCCCAGGCCTCTGCTCTT GACCTCACTCGACAGCTGGTCCACATCTTTGCTCATGAGCCTGCCCACTTTCCCCCAATTGA GGCCCTCTTCCTGCTCGTCACCTCCGTCACACTCACTCTCTTCCAGCAAGGGCCCAGGGATC ATCCTGATATTGTTGATTCATTTATGCAACTCCTGGCACAGGCTCTGAAGCGGAAGCCAGAT TTGTTCCTGTGTGAACGATTGGATGTCAAATCTGTGTTCCAGTGTGCTGTGCTGGCCCTCAA GTTCCCTGAGGCACCTACTGTCAAGGCCTCCTGTGGCTTCTTTACAGAGCTGCTGCCTCGGT GTGGGGAAGTAGAGTCTGTGGGAAAGGTGGTACAGGAAGACGGTCGTATGCTGCTCATAGCA GTGCTGGAGGCCATTGGGGGCCAGGCCTCCCGCAGCCTCATGGACTGCTTTGCCGATATCCT GTTCGCCCTGAACAAGCACTGCTTCAGCCTCCTGAGCATGTGGATCAAGGAGGCCCTGCAGC CACCTGGTTTCCCCTCTGCCCGCCTCAGCCCTGAACAGAAGGATACCTTCAGCCAGCAGATC CTTCGCGAGCGAGTGAACAAGAGGCGGGTGAAGGAGATGGTGAAGGAGTTCACACTGCTGTG CCGGGGTCTCCATGGCACAGATTACACAGCTGACTACTGA (SEQ ID NO:6) Example 4: Exemplary IPO4 Sequences Amino acid sequence of an exemplary IPO4 polypeptide MESAGLEQLLRELLLPDTERIRRATEQLQIVLRAPAALPALCDLLASAADPQIRQFAAVLTR RRLNTRWRRLAAEQRESLKSLILTALQRETEHCVSLSLAQLSATIFRKEGLEAWPQLLQLLQ HSTHSPHSPEREMGLLLLSVVVTSRPEAFQPHHRELLRLLNETLGEVGSPGLLFYSLRTLTT MAPYLSTEDVPLARMLVPKLIMAMQTLIPIDEAKACEALEALDELLESEVPVITPYLSEVLT FCLEVARNVALGNAIRIRILCCLTFLVKVKSKALLKNRLLPPLLHTLFPIVAAEPPPGQLDP EDQDSEEEELEIELMGETPKHFAVQVVDMLALHLPPEKLCPQLMPMLEEALRSESPYQRKAG LLVLAVLSDGAGDHIRQRLLPPLLQIVCKGLEDPSQVVRNAALFALGQFSENLQPHISSYSR EVMPLLLAYLKSVPLGHTHHLAKACYALENFVENLGPKVQPYLPELMECMLQLLRNPSSPRA KELAVSALGAIATAAQASLLPYFPAIMEHLREFLLTGREDLQPVQIQSLETLGVLARAVGEP MRPLAEECCQLGLGLCDQVDDPDLRRCTYSLFAALSGLMGEGLAPHLEQITTLMLLSLRSTE GIVPQYDGSSSFLLFDDESDGEEEEELMDEDVEEEDDSEISGYSVENAFFDEKEDTCAAVGE ISVNTSVAFLPYMESVFEEVFKLLECPHLNVRKAAHEALGQFCCALHKACQSCPSEPNTAAL Attorney Docket No.07039-2180WO1 / 2022-349 QAALARVVPSYMQAVNRERERQVVMAVLEALTGVLRSCGTLTLKPPGRLAELCGVLKAVLQR KTACQDTDEEEEEEDDDQAEYDAMLLEHAGEAIPALAAAAGGDSFAPFFAGFLPLLVCKTKQ GCTVAEKSFAVGTLAETIQGLGAASAQFVSRLLPVLLSTAQEADPEVRSNAIFGMGVLAEHG GHPAQEHFPKLLGLLFPLLARERHDRVRDNICGALARLLMASPTRKPEPQVLAALLHALPLK EDLEEWVTIGRLFSFLYQSSPDQVIDVAPELLRICSLILADNKIPPDTKAALLLLLTFLAKQ HTDSFQAALGSLPVDKAQELQAVLGLS (SEQ ID NO:80) Nucleotide sequence of a nucleic acid encoding an exemplary IPO4 polypeptide ATGGAGTCAGCCGGGCTAGAGCAGCTCCTACGGGAGCTGCTGCTACCGGACACCGAGCGCAT CCGTCGGGCCACGGAACAGCTCCAGATCGTTCTTCGGGCCCCCGCCGCTTTGCCGGCTCTCT GCGACCTGCTAGCCTCGGCGGCCGACCCCCAGATCCGCCAGTTTGCGGCCGTGCTGACCCGC AGACGACTGAACACCCGCTGGCGACGGCTGGCGGCGGAGCAACGGGAGAGCCTCAAGTCCCT GATCCTGACGGCCCTGCAGAGAGAAACAGAGCACTGTGTGAGCCTCAGCCTGGCCCAGCTCT CAGCCACCATTTTTCGAAAGGAAGGCTTGGAGGCCTGGCCACAGCTTTTGCAGCTGCTTCAG CACAGTACCCACAGCCCCCACAGCCCAGAGAGAGAGATGGGGCTTTTGCTGCTAAGTGTGGT GGTGACCTCCCGGCCCGAGGCCTTCCAACCCCACCACCGGGAGCTTCTTCGGCTTCTGAATG AGACTCTTGGTGAGGTGGGCTCTCCTGGGCTGCTCTTCTACTCCCTGCGCACTCTGACCACC ATGGCTCCCTACCTCAGCACTGAAGATGTGCCTCTCGCTCGGATGTTGGTGCCCAAGCTGAT CATGGCCATGCAGACTCTGATCCCCATAGATGAGGCAAAGGCCTGTGAGGCCCTTGAGGCTT TGGATGAACTGTTGGAGTCAGAGGTGCCGGTCATCACCCCCTACCTCTCTGAAGTCCTCACA TTCTGCCTGGAGGTAGCTAGAAATGTGGCCCTGGGCAATGCGATACGCATACGTATTCTCTG CTGCCTCACTTTCTTGGTCAAAGTCAAGAGCAAGGCCTTACTGAAGAATCGTCTCCTGCCAC CCTTGCTGCACACCCTTTTCCCCATTGTGGCTGCTGAGCCCCCACCAGGCCAGTTGGATCCC GAGGACCAGGATTCAGAAGAGGAAGAGTTGGAGATTGAGCTGATGGGGGAGACTCCCAAGCA TTTCGCTGTACAAGTTGTGGACATGCTGGCACTACACCTGCCCCCCGAGAAGCTCTGTCCCC AGCTGATGCCCATGTTGGAAGAGGCTTTGCGGAGCGAGAGCCCATACCAGCGCAAAGCTGGA CTCCTGGTGCTGGCCGTGCTGTCTGACGGAGCTGGCGACCACATCAGGCAGAGACTGCTGCC CCCACTGCTGCAGATTGTGTGCAAGGGCCTGGAGGACCCCTCGCAAGTTGTACGCAATGCTG CGCTGTTTGCCCTGGGCCAGTTCTCAGAAAACCTACAGCCCCATATCAGCAGCTATTCAAGG GAGGTAATGCCACTGCTCCTCGCCTACTTGAAGTCGGTGCCTCTTGGACACACACACCACCT AGCCAAGGCCTGCTATGCCCTGGAGAATTTTGTGGAGAACCTAGGGCCCAAGGTGCAGCCCT ACCTTCCGGAGCTTATGGAATGCATGCTGCAGCTTCTGAGGAACCCCAGCAGTCCCCGGGCC AAGGAGCTGGCTGTGAGCGCCCTGGGAGCCATTGCTACGGCTGCCCAGGCCTCGCTGCTGCC CTACTTCCCTGCCATCATGGAGCACCTGCGGGAATTCCTGTTAACAGGCCGTGAGGACCTTC AGCCTGTGCAGATCCAGAGCCTGGAGACACTGGGGGTGCTGGCACGAGCAGTGGGGGAGCCC ATGAGGCCGCTGGCTGAGGAATGCTGCCAGCTGGGTCTGGGCCTCTGCGACCAGGTAGACGA CCCTGACTTGCGGCGCTGCACGTACAGCCTATTTGCAGCCTTATCGGGTCTGATGGGTGAGG GCCTGGCGCCCCACTTGGAACAGATCACCACGCTCATGCTGCTGTCACTGCGTTCCACCGAG Attorney Docket No.07039-2180WO1 / 2022-349 GGCATTGTGCCTCAGTATGACGGGAGCAGCTCCTTCCTTCTGTTTGACGATGAGAGTGATGG GGAAGAAGAGGAGGAGCTCATGGATGAGGATGTGGAAGAAGAGGATGACTCAGAGATCTCAG GGTACAGCGTGGAGAATGCCTTCTTCGATGAGAAGGAAGACACCTGTGCTGCCGTGGGGGAG ATCTCTGTGAACACCAGTGTGGCCTTCCTTCCATACATGGAAAGTGTCTTTGAAGAAGTATT TAAACTGCTGGAGTGCCCTCACCTGAATGTGCGGAAGGCAGCCCATGAGGCTCTGGGTCAGT TTTGCTGTGCACTGCACAAGGCCTGTCAAAGCTGCCCCTCGGAACCCAACACTGCTGCTTTG CAGGCTGCCCTGGCCCGAGTCGTGCCATCCTACATGCAGGCAGTGAACAGGGAGCGGGAACG CCAGGTGGTGATGGCCGTGCTGGAGGCCCTGACAGGGGTGCTCCGCAGCTGTGGGACCCTCA CACTGAAGCCCCCTGGGCGCCTCGCTGAGCTCTGTGGCGTGCTCAAGGCTGTGCTGCAGAGG AAGACAGCCTGTCAGGATACTGACGAGGAGGAGGAAGAGGAAGATGATGATCAGGCTGAATA CGACGCCATGTTGCTGGAGCACGCTGGAGAGGCCATCCCTGCCCTGGCAGCCGCGGCTGGGG GAGACTCCTTTGCCCCATTCTTTGCCGGTTTCCTGCCATTATTGGTGTGCAAGACAAAACAG GGCTGCACAGTGGCAGAGAAGTCCTTTGCAGTGGGGACCTTGGCAGAGACTATTCAGGGCCT GGGTGCTGCCTCAGCCCAGTTTGTGTCTCGGCTGCTCCCTGTGCTGTTGAGCACCGCCCAAG AGGCAGACCCCGAGGTGCGAAGCAATGCCATCTTCGGGATGGGCGTGCTGGCAGAGCATGGG GGCCACCCTGCCCAGGAACACTTCCCCAAGCTGCTGGGGCTCCTTTTTCCCCTCCTGGCGCG GGAGCGACATGATCGTGTCCGTGACAACATCTGTGGGGCACTTGCCCGCCTGTTGATGGCCA GTCCCACCAGGAAACCAGAGCCCCAGGTGCTGGCTGCCCTACTGCATGCCCTGCCACTGAAG GAGGACTTGGAGGAGTGGGTCACCATTGGGCGCCTCTTCAGCTTCCTGTACCAGAGCAGCCC TGACCAGGTTATAGATGTGGCTCCCGAGCTTCTGCGTATCTGCAGCCTCATTCTGGCTGACA ACAAGATCCCACCAGACACCAAGGCCGCACTGTTGCTGCTCCTGACGTTCCTGGCCAAACAG CACACCGACAGCTTTCAAGCAGCTCTGGGCTCACTGCCTGTTGACAAGGCTCAGGAGCTCCA GGCTGTACTGGGCCTCTCCTAG (SEQ ID NO:81) Example 5: Exemplary IPO11 Sequences Amino acid sequence of an exemplary IPO11 polypeptide MDLNSASTVVLQVLTQATSQDTAVLKPAEEQLKQWETQPGFYSVLLNIFTNHTLDINVRWLA VLYFKHGIDRYWRRVAPHALSEEEKTTLRAGLITNFNEPINQIATQIAVLIAKVARLDCPRQ WPELIPTLIESVKVQDDLRQHRALLTFYHVTKTLASKRLAADRKLFYDLASGIYNFACSLWN HHTDTFLQEVSSGNEAAILSSLERTLLSLKVLRKLTVNGFVEPHKNMEVMGFLHGIFERLKQ FLECSRSIGTDNVCRDRLEKTIILFTKVLLDFLDQHPFSFTPLIQRSLEFSVSYVFTEVGEG VTFERFIVQCMNLIKMIVKNYAYKPSKNFEDSSPETLEAHKIKMAFFTYPTLTEICRRLVSH YFLLTEEELTMWEEDPEGFTVEETGGDSWKYSLRPCTEVLFIDIFHEYNQTLTPVLLEMMQT LQGPTNVEDMNALLIKDAVYNAVGLAAYELFDSVDFDQWFKNQLLPELQVIHNRYKPLRRRV IWLIGQWISVKFKSDLRPMLYEAICNLLQDQDLVVRIETATTLKLTVDDFEFRTDQFLPYLE TMFTLLFQLLQQVTECDTKMHVLHVLSCVIERVNMQIRPYVGCLVQYLPLLWKQSEEHNMLR CAILTTLIHLVQGLGADSKNLYPFLLPVIQLSTDVSQPPHVYLLEDGLELWLVTLENSPCIT Attorney Docket No.07039-2180WO1 / 2022-349 PELLRIFQNMSPLLELSSENLRTCFKIINGYIFLSSTEFLQTYAVGLCQSFCELLKEITTEG QVQVLKVVENALKVNPILGPQMFQPILPYVFKGIIEGERYPVVMSTYLGVMGRVLLQNTSFF SSLLNEMAHKFNQEMDQLLGNMIEMWVDRMDNITQPERRKLSALALLSLLPSDNSVIQDKFC GIINISVEGLHDVMTEDPETGTYKDCMLMSHLEEPKVTEDEEPPTEQDKRKKMLALKDPVHT VSLQQFIYEKLKAQQEMLGEQGFQSLMETVDTEIVTQLQEFLQGF (SEQ ID NO:82) Nucleotide sequence of a nucleic acid encoding an exemplary IPO11 polypeptide ATGGATCTCAATAGTGCCAGCACTGTTGTTCTTCAGGTGTTAACACAGGCCACCAGTCAGGA TACTGCTGTGTTAAAACCAGCTGAGGAGCAGTTGAAGCAGTGGGAGACACAGCCAGGTTTCT ATTCAGTGTTGCTGAATATTTTCACCAACCACACTTTGGATATAAATGTAAGGTGGCTTGCT GTACTGTATTTTAAACATGGAATTGATCGCTACTGGAGACGTGTAGCACCTCATGCTCTCTC AGAGGAGGAGAAAACTACTCTGCGTGCAGGGCTCATCACCAACTTCAATGAACCAATAAACC AGATTGCAACTCAGATTGCAGTGCTCATTGCAAAAGTTGCTAGATTGGATTGTCCCAGACAG TGGCCTGAACTAATTCCCACTCTTATAGAGTCTGTTAAAGTCCAGGATGATCTTCGACAGCA CAGAGCATTACTTACCTTCTATCATGTTACCAAGACACTGGCATCTAAACGACTTGCTGCTG ATAGAAAACTATTTTATGATTTAGCTTCTGGAATTTATAATTTTGCCTGCTCTCTGTGGAAT CACCACACAGACACATTCCTGCAAGAAGTTTCTTCTGGCAATGAAGCTGCAATTTTGAGTTC ACTAGAACGAACACTGCTATCATTGAAAGTGCTGCGTAAGTTAACTGTTAATGGATTTGTGG AACCTCATAAGAATATGGAGGTGATGGGTTTTTTACATGGAATATTTGAACGTCTAAAACAG TTTCTGGAATGCAGTAGAAGTATAGGTACAGATAATGTGTGTAGAGATAGACTGGAAAAGAC CATCATTCTTTTTACTAAAGTGCTTTTGGACTTCTTGGATCAGCATCCTTTTTCATTTACTC CTCTAATTCAGAGATCACTGGAATTTTCTGTAAGCTATGTTTTTACAGAAGTTGGTGAAGGC GTTACATTTGAACGATTCATTGTCCAATGTATGAATCTTATTAAGATGATTGTCAAAAATTA TGCTTATAAGCCATCCAAAAATTTTGAAGATAGCAGCCCTGAAACTCTTGAAGCCCATAAGA TTAAGATGGCATTCTTCACATATCCTACTTTGACAGAGATATGTAGAAGATTAGTCTCTCAT TATTTCCTATTAACTGAAGAAGAACTGACAATGTGGGAAGAAGACCCAGAAGGCTTTACAGT GGAAGAAACAGGAGGAGATTCTTGGAAATATAGTTTGAGGCCATGCACTGAAGTATTATTTA TAGATATATTCCATGAATATAATCAGACTCTTACTCCTGTACTTCTAGAAATGATGCAAACA CTTCAAGGACCCACAAATGTGGAAGATATGAATGCACTGTTAATCAAAGATGCTGTGTATAA TGCTGTTGGATTAGCTGCTTATGAGCTCTTTGACAGTGTTGATTTTGATCAGTGGTTTAAAA ACCAGCTTCTTCCAGAATTACAAGTCATTCACAATAGGTATAAGCCATTGCGACGCAGGGTG ATTTGGCTCATCGGTCAGTGGATTTCTGTGAAATTCAAGTCTGACTTAAGACCCATGCTTTA TGAAGCAATCTGTAACTTGCTTCAAGATCAAGATTTAGTGGTCCGTATTGAAACAGCTACAA CTTTGAAGTTAACTGTTGATGATTTTGAATTTAGAACAGATCAGTTTCTACCGTATTTGGAA ACCATGTTCACACTACTTTTTCAGTTACTGCAGCAAGTTACAGAATGTGACACAAAGATGCA TGTTTTGCATGTCCTTTCTTGTGTGATCGAAAGAGTCAACATGCAGATACGACCATATGTGG GATGTTTGGTACAATATTTGCCCCTCCTTTGGAAGCAGAGTGAAGAACACAATATGTTGAGA TGTGCTATTTTGACAACACTTATTCATCTTGTTCAGGGATTAGGAGCAGACAGCAAGAACCT Attorney Docket No.07039-2180WO1 / 2022-349 GTACCCTTTCCTGCTCCCAGTTATTCAACTGAGTACAGATGTTTCACAGCCTCCACATGTTT ATCTTCTGGAAGATGGTTTAGAATTATGGTTAGTAACTTTGGAAAACAGTCCATGTATTACA CCAGAGTTGCTTCGTATATTTCAGAATATGTCACCACTTCTTGAACTAAGTTCAGAAAATCT TAGAACTTGCTTTAAGATCATCAATGGTTATATCTTTTTATCATCAACAGAATTTTTACAGA CATACGCAGTAGGTCTATGCCAGTCCTTTTGTGAACTTTTAAAGGAAATTACTACAGAAGGT CAAGTTCAGGTGCTCAAGGTTGTGGAAAATGCCCTTAAAGTGAACCCAATACTAGGTCCACA AATGTTTCAACCGATTTTACCCTATGTTTTCAAGGGTATTATAGAAGGGGAGAGGTATCCTG TAGTGATGTCCACGTATCTTGGAGTTATGGGTCGAGTTCTACTACAAAACACTAGTTTTTTT TCTTCACTACTTAATGAGATGGCCCATAAATTTAATCAGGAGATGGACCAGCTTTTGGGAAA TATGATTGAAATGTGGGTTGATCGAATGGACAACATTACCCAGCCTGAAAGAAGAAAACTTT CAGCTTTGGCTTTGCTCTCTCTTCTGCCATCTGATAATAGTGTTATCCAAGATAAATTCTGT GGGATTATAAACATTTCAGTAGAAGGCCTGCATGATGTCATGACGGAAGATCCTGAAACAGG AACTTATAAAGACTGTATGTTGATGTCTCATCTTGAGGAACCAAAAGTAACAGAAGATGAAG AACCACCCACAGAACAAGATAAGAGGAAAAAGATGCTGGCCCTGAAGGACCCTGTTCATACA GTGTCACTGCAGCAGTTCATCTACGAGAAGCTCAAGGCACAGCAGGAGATGCTAGGAGAACA AGGTTTCCAGTCCCTCATGGAAACAGTGGATACGGAGATTGTCACCCAGCTACAGGAGTTTT TGCAAGGATTCTAA (SEQ ID NO:83) Example 6: Exemplary IPO12 Sequences Amino acid sequence of an exemplary IPO12 polypeptide MEGAKPTLQLVYQAVQALYHDPDPSGKERASFWLGELQRSVHAWEISDQLLQIRQDVESCYF AAQTMKMKIQTSFYELPTDSHASLRDSLLTHIQNLKDLSPVIVTQLALAIADLALQMPSWKG CVQTLVEKYSNDVTSLPFLLEILTVLPEEVHSRSLRIGANRRTEIIEDLAFYSSTVVSLLMT CVEKAGTDEKMLMKVFRCLGSWFNLGVLDSNFMANNKLLALLFEVLQQDKTSSNLHEAASDC VCSALYAIENVETNLPLAMQLFQGVLTLETAYHMAVAREDLDKVLNYCRIFTELCETFLEKI VCTPGQGLGDLRTLELLLICAGHPQYEVVEISFNFWYRLGEHLYKTNDEVIHGIFKAYIQRL LHALARHCQLEPDHEGVPEETDDFGEFRMRVSDLVKDLIFLIGSMECFAQLYSTLKEGNPPW EVTEAVLFIMAAIAKSVDPENNPTLVEVLEGVVRLPETVHTAVRYTSIELVGEMSEVVDRNP QFLDPVLGYLMKGLCEKPLASAAAKAIHNICSVCRDHMAQHFNGLLEIARSLDSFLLSPEAA VGLLKGTALVLARLPLDKITECLSELCSVQVMALKKLLSQEPSNGISSDPTVFLDRLAVIFR HTNPIVENGQTHPCQKVIQEIWPVLSETLNKHRADNRIVERCCRCLRFAVRCVGKGSAALLQ PLVTQMVNVYHVHQHSCFLYLGSILVDEYGMEEGCRQGLLDMLQALCIPTFQLLEQQNGLQN HPDTVDDLFRLATRFIQRSPVTLLRSQVVIPILQWAIASTTLDHRDANCSVMRFLRDLIHTG VANDHEEDFELRKELIGQVMNQLGQQLVSQLLHTCCFCLPPYTLPDVAEVLWEIMQVDRPTF CRWLENSLKGLPKETTVGAVTVTHKQLTDFHKQVTSAEECKQVCWALRDFTRLFR (SEQ ID NO:84) Attorney Docket No.07039-2180WO1 / 2022-349 Nucleotide sequence of a nucleic acid encoding an exemplary IPO12 polypeptide ATGGAAGGAGCAAAGCCGACATTGCAGCTCGTGTACCAGGCAGTGCAGGCGCTTTACCACGA CCCAGATCCCAGCGGAAAGGAGCGCGCCTCTTTTTGGCTTGGGGAGCTGCAGCGTTCGGTTC ATGCATGGGAGATCTCAGACCAGTTGTTACAGATCCGGCAGGATGTGGAGTCATGCTATTTT GCTGCACAGACCATGAAAATGAAGATTCAGACCTCATTTTATGAGCTCCCCACAGACTCTCA TGCCTCTTTACGGGACTCATTGCTAACCCATATCCAGAACTTGAAAGACTTGTCACCTGTTA TTGTAACGCAGCTGGCTTTAGCAATAGCAGATCTTGCCCTACAGATGCCTTCCTGGAAGGGA TGTGTGCAAACACTGGTGGAAAAATACAGCAATGATGTGACTTCTTTGCCTTTTTTGCTGGA GATCCTTACAGTGTTACCTGAAGAAGTACATAGTCGTTCCTTACGAATTGGAGCTAATCGGC GCACAGAAATTATAGAAGATTTGGCCTTCTACTCTAGTACAGTAGTATCTCTATTGATGACC TGTGTAGAAAAAGCAGGAACAGATGAGAAAATGCTTATGAAGGTTTTTCGCTGTTTGGGAAG TTGGTTTAACTTGGGAGTTTTGGACAGTAACTTCATGGCTAACAATAAATTACTAGCACTCC TTTTTGAGGTTTTGCAACAGGATAAGACCTCGTCTAACCTACATGAAGCTGCTTCGGACTGT GTATGCTCAGCTCTCTATGCCATTGAGAATGTGGAGACTAACTTGCCATTAGCCATGCAACT TTTTCAGGGAGTGCTGACATTGGAGACTGCCTATCATATGGCCGTGGCACGTGAAGATTTAG ACAAAGTTCTGAATTACTGCCGTATTTTCACTGAACTATGTGAAACTTTTCTTGAAAAAATT GTTTGTACTCCAGGCCAAGGTCTTGGGGACCTTCGAACTCTGGAGCTGCTGCTTATCTGTGC AGGCCATCCTCAATATGAGGTAGTAGAAATTTCATTTAACTTTTGGTACCGACTGGGGGAAC ATTTGTACAAAACTAACGATGAAGTTATTCATGGCATCTTCAAAGCTTACATTCAGAGGCTG CTTCACGCCTTGGCTCGACACTGCCAGCTGGAACCAGACCATGAGGGGGTTCCTGAGGAGAC TGATGACTTTGGGGAGTTTCGCATGAGGGTATCAGACCTGGTAAAGGACTTGATTTTCTTGA TAGGGTCTATGGAGTGTTTTGCTCAGTTATATTCTACTCTGAAAGAAGGCAACCCACCCTGG GAGGTGACAGAAGCGGTTCTCTTTATCATGGCTGCTATAGCAAAGAGTGTTGATCCGGAAAA CAATCCAACACTTGTGGAAGTCCTAGAAGGAGTTGTCCGCCTCCCGGAGACCGTACATACGG CTGTGCGATACACCAGCATTGAATTGGTTGGAGAGATGAGTGAAGTCGTTGATCGAAATCCT CAGTTCCTTGACCCTGTGTTGGGCTATTTGATGAAAGGCCTGTGTGAAAAGCCCCTGGCTTC TGCTGCAGCCAAAGCCATTCATAACATTTGCTCTGTCTGCCGAGATCACATGGCTCAGCACT TTAATGGACTCCTGGAGATTGCCCGCTCCCTCGATTCCTTCCTGTTGTCTCCAGAAGCTGCT GTGGGCTTGCTAAAAGGGACAGCACTTGTCCTAGCCCGATTACCTTTGGATAAGATTACCGA ATGTCTTAGTGAACTATGTTCTGTTCAGGTTATGGCATTGAAAAAGCTGTTGTCTCAAGAGC CCAGCAATGGCATATCCTCAGATCCCACAGTGTTCTTAGATCGCCTTGCAGTGATATTTAGG CATACCAATCCCATTGTGGAAAATGGACAGACTCATCCGTGTCAGAAAGTCATACAGGAAAT ATGGCCAGTTTTATCCGAGACTCTAAATAAGCACCGAGCTGATAATCGGATTGTAGAGCGTT GTTGCAGGTGCCTGCGCTTTGCTGTTCGCTGTGTAGGCAAAGGATCTGCAGCACTGCTGCAG CCACTAGTCACACAGATGGTGAATGTGTACCACGTACATCAGCATTCCTGCTTCCTGTACCT TGGCAGTATCCTTGTGGATGAATATGGCATGGAAGAAGGCTGTCGGCAGGGACTGCTAGACA TGCTCCAGGCACTGTGCATCCCCACCTTTCAGCTCCTAGAACAGCAGAATGGTCTCCAGAAT CACCCTGACACTGTAGATGACCTGTTCCGGCTAGCCACCAGGTTTATTCAGCGTAGCCCTGT CACCTTGCTGCGGAGCCAAGTGGTCATCCCTATCTTACAGTGGGCCATTGCCTCTACTACCC Attorney Docket No.07039-2180WO1 / 2022-349 TGGACCACCGGGATGCCAATTGTAGTGTCATGAGGTTTCTACGAGACCTCATTCATACAGGG GTAGCCAATGATCATGAAGAAGACTTTGAATTACGGAAAGAACTGATTGGACAGGTGATGAA CCAGCTTGGACAGCAGCTTGTCAGCCAGCTGCTGCACACCTGCTGCTTTTGCCTCCCCCCCT ATACCCTACCAGATGTGGCTGAAGTGCTCTGGGAGATCATGCAGGTTGACAGACCGACTTTT TGTCGATGGTTAGAAAATTCCTTAAAAGGTTTGCCAAAGGAAACAACCGTGGGAGCCGTCAC AGTGACACACAAACAACTTACAGACTTCCACAAGCAAGTCACTAGTGCTGAGGAATGTAAAC AAGTTTGCTGGGCCTTGCGAGACTTCACCAGGTTGTTTCGATAG (SEQ ID NO:85) Example 7: Karyopherin polypeptides can reduce tau polypeptide accumulation A screen for import receptors that can reduce tau polypeptide aggregation was performed. An expression construct encoding a GFP-tagged aggregation-prone mutant of tau was expressed in HEK293T cells together with an expression construct encoding an mCherry-tagged KPNB1, KPNB2, IPO3A, IPO38, IPO4, IPO7, IPO8, IPO9, IPO11, IPO12, or IPO13. Expression of KPNB1, IPO3A, IPO3B, IPO4, IPO11, IPO12, and IPO13 polypeptides reduced total tau polypeptide levels and hyperphosphorylated tau polypeptide levels in the detergent-insoluble fraction (Figures 2A-2D). The aggregation-prone mutant tau (Tau^3xmut) polypeptide used was a triple mutant tau polypeptide variant containing a A152T amino acid substitution, a P301L amino acid substitution, and a S320F amino acid substitution. Tau^3xmut polypeptides expressed in HEK293T cells induced mislocalization of endogenous FG nucleoporins (Figure 3). Organotypic brain slice cultures (BSCs) were used to model tau pathology. Brains were collected from either C57Bl/6 or hTauKI mice aged P8/9, bisecting the hippocampus and cortex. Tissue was cut into 350 ?m coronal slices and was maintained in tissue culture inserts in 6-well plates. HEK293T cells were co-transfected with mutant tau polypeptide, AAV-EGFP-hTau24 expression constructs, and AAV packaging constructs.48 hours after transfection, cell supernatant containing packaged AAV particles was added to brain slices to transduce the brain slices. Tissues were stained for microscopy to assess amyloid inclusions and phospho-tau pathology between days in vitro (DIV). Biochemical analysis was performed to assay for detergent-insoluble inclusions. BSCs transduced with AAV-EGFP- Tau^3xMut formed fibrillar inclusions that were positive for phospho-tau polypeptides (Figure 4A). BSCs transduced with AAV-EGFP-Tau^3xMut also formed amyloid stain positive Attorney Docket No.07039-2180WO1 / 2022-349 aggregates (Figure 4B and Figure 5A). Hyperphosphorylated mutant tau polypeptides were seen in both the soluble and insoluble fraction (Figure 5B). BSCs transduced with AAV- EGFP-Tau^WT did not form fibrillar inclusions that were positive for phospho-tau polypeptides or amyloid stains. Tau polypeptide fibrils were obtained from Alzheimer’s disease patients. The demographics and neuropathological data of the Alzheimer’s disease patients are in Table 3. Table 3. Group PathDx LBD Braak Thal TDP ClinicalDx Dur Age Sex Area Phospho-tau polypeptide pathology was confirmed in the Alzheimer’s disease patient samples via immunohistochemistry. Electron microscopy showed sarkosyl-insoluble tau polypeptides in Alzheimer’s disease patient samples (Figure 6A). Western blot analysis was used to confirm the presence of phospho-tau polypeptides in Alzheimer’s disease patient samples, using a phospho-tau specific antibody (AT8) (Figure 6B). Tau polypeptide fibrils obtained from Alzheimer’s disease patients were seeded onto cells to establish a physiological model of Alzheimer’s disease tauopathy. A high-low-high spin centrifugation extraction method (HLH) was used to obtain sarkosyl-insoluble tau polypeptides from Alzheimer’s disease patient samples, and the sarkosyl-insoluble tau Attorney Docket No.07039-2180WO1 / 2022-349 polypeptides were seeded into cultured Tau RD P301S cells (ATTC #CRL-3275) (Figure 7A). Immunofluorescence images show that adding sarkosyl-insoluble tau seeds induced the aggregation of fluorescent protein-tagged tau polypeptides within the cells (Figure 7B). Example 8: C-terminal IP13 fragments reduced tau aggregation pathology This Example identifies a role for fragments of an IPO13 polypeptide in reducing tau aggregation. Fragments of an IPO13 polypeptide evaluated included full length IPO13, IPO13 N- ter (H1-10), IPO13 C-ter (H11-20), H1-11, H1-15, H1-19, H2-20, H4-20, H7-20, H9-20, and IPO13?aa1-22. The activity of IPO13 was stronger in the C-terminal fragments, including H7-20, H9-20, and H11-20 (Figure 8). Furthermore, immunohistochemistry analysis demonstrated that full length IP13 and C-terminal IPO13 fragments reduced the accumulation of hyperphosphorylated tau aggregates (Figure 9). To test the activity of NIRs, Alzheimer’s disease (AD) patient-derived tau seeds were co-delivered into the Tau RD P301 reporter cell line with expression plasmids encoding mCherry-tagged NIRs using Lipofectamine LTX. Successful co-delivery of AD brain tissue derived tau seeds together with an expression plasmid encoding mCherry led to the formation of foci indicating seeding-induced tau aggregation in cells that also expressed mCherry. The study showed that replacing expression plasmids encoding mCherry with expression plasmids encoding mCherry-tagged KPNB1, IPO4, or KPNB1 reduced the formation of tau aggregates (Figure 10 and Figure 11A). KPNB1 had a modest effect on tau aggregation, while IPO4 and IPO13 strongly reduced insoluble and hyperphosphorylated tau levels for the triple mutant tau construct. Cells without the added tau seeds did not form YFP-positive tau aggregates (Figure 11B). Example 9: Treating Alzheimer’s Disease A human identified as having, or as being at risk of developing, Alzheimer’s Disease is administered one or more KPNB1 polypeptides or fragments thereof. The administered KPNB1 polypeptides or fragments thereof can slow, delay, reverse, or prevent progression of neurodegeneration in the brain of the human. Attorney Docket No.07039-2180WO1 / 2022-349 Example 10: Treating Alzheimer’s Disease A human identified as having, or as being at risk of developing, Alzheimer’s Disease is administered nucleic acid encoding a KPNB1 polypeptide or a fragment thereof. The administered nucleic acid can encode the KPNB1 polypeptide or the fragment thereof within the brain of the human to slow, delay, reverse, or prevent progression of neurodegeneration in the brain of the human. Example 11: Exemplary Embodiments Embodiment 1. A method for treating a mammal having a tauopathy, wherein said method comprises administering a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide to said mammal. Embodiment 2. The method of embodiment 1, wherein said KPNB1 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. Embodiment 3. The method of embodiment 2, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. Embodiment 4. The method of any one of embodiments 1-3, wherein said method comprises identifying said mammal as being in need of said KPNB1 polypeptide or said fragment prior to said administering step. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 5. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide to said mammal. Embodiment 6. The method of any one of embodiments 1-5, wherein said method comprises administering said KPNB1 polypeptide to said mammal. Embodiment 7. The method of any one of embodiments 1-5, wherein said method comprises administering said fragment of said KPNB1 polypeptide to said mammal. Embodiment 8. The method of embodiment 7, wherein said fragment of said KPNB1 polypeptide consists of the amino acid sequence set forth in any one of SEQ ID NOs:7-25. Embodiment 9. The method of any one of embodiments 5-8, wherein said method comprises identifying said mammal as being in need of said KPNB1 polypeptide or said fragment prior to said administering step. Embodiment 10. A method for treating a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide to said mammal, wherein said KPNB1 polypeptide or said fragment is expressed by cells in a brain of said mammal. Embodiment 11. The method of embodiment 10, wherein said KPNB1 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. Embodiment 12. The method of embodiment 11, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow Attorney Docket No.07039-2180WO1 / 2022-349 and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. Embodiment 13. The method of any one of embodiments 10-12, wherein said method comprises identifying said mammal as being in need of said nucleic acid prior to said administering step. Embodiment 14. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide to said mammal wherein said KPNB1 polypeptide or said fragment is expressed by cells in a brain of said mammal. Embodiment 15. The method of embodiment 14, wherein said method comprises identifying said mammal as being in need of said nucleic acid prior to said administering step. Embodiment 16. The method of any one of embodiments 10-14, wherein said nucleic acid encodes said KPNB1 polypeptide. Embodiment 17. The method of any one of embodiments 10-14, wherein said nucleic acid encodes said fragment of said KPNB1 polypeptide. Embodiment 18. The method of embodiment 17, wherein said fragment of said KPNB1 polypeptide consists of the amino acid sequence set forth in any one of SEQ ID NOs:7-25. Embodiment 19. The method of any one of embodiments 10-18, wherein said nucleic acid is in the form of a vector. Embodiment 20. The method of embodiment 19, wherein said vector is an AAV vector. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 21. The method of embodiment 19, wherein said vector is an expression plasmid. Embodiment 22. The method of any one of embodiments 1-21, wherein said mammal is a human. Embodiment 23. The method of any one of embodiments 1-22, wherein said tauopathy is selected from the group consisting of Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, and primary age-related tauopathy. Embodiment 24. The method of any one of embodiments 1-23, wherein said administering comprises intracerebral injection. Embodiment 25. The use of a composition comprising a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide to treat a mammal having a tauopathy. Embodiment 26. A KPNB1 polypeptide or a fragment of said KPNB1 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. Embodiment 27. A KPNB1 polypeptide or a fragment of said KPNB1 polypeptide for use in the treatment of a tauopathy. Embodiment 28. The use of a composition comprising nucleic acid encoding a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide to treat a mammal having a tauopathy. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 29. Nucleic acid encoding a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. Embodiment 30. Nucleic acid encoding a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide for use in the treatment of a tauopathy. Embodiment 31. A method for treating a mammal having a tauopathy, wherein said method comprises administering an IPO3 polypeptide or a fragment of said IPO3 polypeptide to said mammal. Embodiment 32. The method of embodiment 31, wherein said IPO3 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. Embodiment 33. The method of embodiment 32, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. Embodiment 34. The method of any one of embodiments 31-33, wherein said method comprises identifying said mammal as being in need of said IPO3 polypeptide or said fragment prior to said administering step. Embodiment 35. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering an IPO3 polypeptide or a fragment of said IPO3 polypeptide to said mammal. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 36. The method of any one of embodiments 31-35, wherein said method comprises administering said IPO3 polypeptide to said mammal. Embodiment 37. The method of any one of embodiments 31-35, wherein said method comprises administering said fragment of said IPO3 polypeptide to said mammal. Embodiment 38. The method of embodiment 37, wherein said fragment of said IPO3 polypeptide consists of the amino acid sequence set forth in any one of SEQ ID NOs:26-55. Embodiment 39. The method of any one of embodiments 35-38, wherein said method comprises identifying said mammal as being in need of said IPO3 polypeptide or said fragment prior to said administering step. Embodiment 40. A method for treating a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO3 polypeptide or a fragment of said IPO3 polypeptide to said mammal, wherein said IPO3 polypeptide or said fragment is expressed by cells in a brain of said mammal. Embodiment 41. The method of embodiment 40, wherein said IPO3 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. Embodiment 42. The method of embodiment 41, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 43. The method of any one of embodiments 40-42, wherein said method comprises identifying said mammal as being in need of said nucleic acid prior to said administering step. Embodiment 44. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO3 polypeptide or a fragment of said IPO3 polypeptide to said mammal wherein said IPO3 polypeptide or said fragment is expressed by cells in a brain of said mammal. Embodiment 45. The method of embodiment 44, wherein said method comprises identifying said mammal as being in need of said nucleic acid prior to said administering step. Embodiment 46. The method of any one of embodiments 40-44, wherein said nucleic acid encodes said IPO3 polypeptide. Embodiment 47. The method of any one of embodiments 40-44, wherein said nucleic acid encodes said fragment of said IPO3 polypeptide. Embodiment 48. The method of embodiment 47, wherein said fragment of said IPO3 polypeptide consists of the amino acid sequence set forth in any one of SEQ ID NOs:26-55. Embodiment 49. The method of any one of embodiments 40-48, wherein said nucleic acid is in the form of a vector. Embodiment 50. The method of embodiment 49, wherein said vector is an AAV vector. Embodiment 51. The method of embodiment 49, wherein said vector is an expression plasmid. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 52. The method of any one of embodiments 31-41, wherein said mammal is a human. Embodiment 53. The method of any one of embodiments 31-42, wherein said tauopathy is selected from the group consisting of Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, and primary age-related tauopathy. Embodiment 54. The method of any one of embodiments 31-43, wherein said administering comprises intracerebral injection. Embodiment 55. The use of a composition comprising an IPO3 polypeptide or a fragment of said IPO3 polypeptide to treat a mammal having a tauopathy. Embodiment 56. An IPO3 polypeptide or a fragment of said IPO3 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. Embodiment 57. An IPO3 polypeptide or a fragment of said IPO3 polypeptide for use in the treatment of a tauopathy. Embodiment 58. The use of a composition comprising nucleic acid encoding an IPO3 polypeptide or a fragment of said IPO3 polypeptide to treat a mammal having a tauopathy. Embodiment 59. Nucleic acid encoding an IPO3 polypeptide or a fragment of said IPO3 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 60. Nucleic acid encoding an IPO3 polypeptide or a fragment of said IPO3 polypeptide for use in the treatment of a tauopathy. Embodiment 61. A method for treating a mammal having a tauopathy, wherein said method comprises administering an IPO13 polypeptide or a fragment of said IPO13 polypeptide to said mammal. Embodiment 62. The method of embodiment 61, wherein said IPO13 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. Embodiment 63. The method of embodiment 62, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. Embodiment 64. The method of any one of embodiments 61-63, wherein said method comprises identifying said mammal as being in need of said IPO13 polypeptide or said fragment prior to said administering step. Embodiment 65. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering an IPO13 polypeptide or a fragment of said IPO13 polypeptide to said mammal. Embodiment 66. The method of any one of embodiments 61-65, wherein said method comprises administering said IPO13 polypeptide to said mammal. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 67. The method of any one of embodiments 61-65, wherein said method comprises administering said fragment of said IPO13 polypeptide to said mammal. Embodiment 68. The method of embodiment 67, wherein said fragment of said IPO13 polypeptide consists of the amino acid sequence set forth in any one of SEQ ID NOs:56-77. Embodiment 69. The method of any one of embodiments 65-68, wherein said method comprises identifying said mammal as being in need of said IPO13 polypeptide or said fragment prior to said administering step. Embodiment 70. A method for treating a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO13 polypeptide or a fragment of said IPO13 polypeptide to said mammal, wherein said IPO13 polypeptide or said fragment is expressed by cells in a brain of said mammal. Embodiment 71. The method of embodiment 70, wherein said IPO13 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. Embodiment 72. The method of embodiment 71, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. Embodiment 73. The method of any one of embodiments 70-72, wherein said method comprises identifying said mammal as being in need of said nucleic acid prior to said administering step. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 74. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO13 polypeptide or a fragment of said IPO13 polypeptide to said mammal wherein said IPO13 polypeptide or said fragment is expressed by cells in a brain of said mammal. Embodiment 75. The method of embodiment 74, wherein said method comprises identifying said mammal as being in need of said nucleic acid prior to said administering step. Embodiment 76. The method of any one of embodiments 70-74, wherein said nucleic acid encodes said IPO13 polypeptide. Embodiment 77. The method of any one of embodiments 70-74, wherein said nucleic acid encodes said fragment of said IPO13 polypeptide. Embodiment 78. The method of embodiment 77, wherein said fragment of said IPO13 polypeptide consists of the amino acid sequence set forth in any one of SEQ ID NOs:56-77. Embodiment 79. The method of any one of embodiments 70-78, wherein said nucleic acid is in the form of a vector. Embodiment 80. The method of embodiment 79, wherein said vector is an AAV vector. Embodiment 81. The method of embodiment 79, wherein said vector is an expression plasmid. Embodiment 82. The method of any one of embodiments 61-81, wherein said mammal is a human. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 83. The method of any one of embodiments 61-82, wherein said tauopathy is selected from the group consisting of Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, and primary age-related tauopathy. Embodiment 84. The method of any one of embodiments 61-83, wherein said administering comprises intracerebral injection. Embodiment 85. The use of a composition comprising an IPO13 polypeptide or a fragment of said IPO13 polypeptide to treat a mammal having a tauopathy. Embodiment 86. An IPO13 polypeptide or a fragment of said IPO13 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. Embodiment 87. An IPO13 polypeptide or a fragment of said IPO13 polypeptide for use in the treatment of a tauopathy. Embodiment 88. The use of a composition comprising nucleic acid encoding an IPO13 polypeptide or a fragment of said IPO13 polypeptide to treat a mammal having a tauopathy. Embodiment 89. Nucleic acid encoding an IPO13 polypeptide or a fragment of said IPO13 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. Embodiment 90. Nucleic acid encoding an IPO13 polypeptide or a fragment of said IPO13 polypeptide for use in the treatment of a tauopathy. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 91. A method for treating a mammal having a tauopathy, wherein said method comprises administering an IPO4 polypeptide or a fragment of said IPO4 polypeptide to said mammal. Embodiment 92. The method of embodiment 91, wherein said IPO4 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. Embodiment 93. The method of embodiment 92, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. Embodiment 94. The method of any one of embodiments 91-93, wherein said method comprises identifying said mammal as being in need of said IPO4 polypeptide or said fragment prior to said administering step. Embodiment 95. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering an IPO4 polypeptide or a fragment of said IPO4 polypeptide to said mammal. Embodiment 96. The method of any one of embodiments 91-95, wherein said method comprises administering said IPO4 polypeptide to said mammal. Embodiment 97. The method of any one of embodiments 91-95, wherein said method comprises administering said fragment of said IPO4 polypeptide to said mammal. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 98. The method of any one of embodiments 95-97, wherein said method comprises identifying said mammal as being in need of said IPO4 polypeptide or said fragment prior to said administering step. Embodiment 99. A method for treating a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO4 polypeptide or a fragment of said IPO4 polypeptide to said mammal, wherein said IPO4 polypeptide or said fragment is expressed by cells in a brain of said mammal. Embodiment 100. The method of embodiment 99, wherein said IPO4 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. Embodiment 101. The method of embodiment 100, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. Embodiment 102. The method of any one of embodiments 99-101, wherein said method comprises identifying said mammal as being in need of said nucleic acid prior to said administering step. Embodiment 103. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO4 polypeptide or a fragment of said IPO4 polypeptide to said mammal wherein said IPO4 polypeptide or said fragment is expressed by cells in a brain of said mammal. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 104. The method of embodiment 103, wherein said method comprises identifying said mammal as being in need of said nucleic acid prior to said administering step. Embodiment 105. The method of any one of embodiments 99-104, wherein said nucleic acid encodes said IPO4 polypeptide. Embodiment 106. The method of any one of embodiments 99-105, wherein said nucleic acid encodes said fragment of said IPO4 polypeptide. Embodiment 107. The method of any one of embodiments 99-106, wherein said nucleic acid is in the form of a vector. Embodiment 108. The method of embodiment 107, wherein said vector is an AAV vector. Embodiment 109. The method of embodiment 107, wherein said vector is an expression plasmid. Embodiment 110. The method of any one of embodiments 91-109, wherein said mammal is a human. Embodiment 111. The method of any one of embodiments 91-110, wherein said tauopathy is selected from the group consisting of Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto- nigral degeneration, and primary age-related tauopathy. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 112. The method of any one of embodiments 91-111, wherein said administering comprises intracerebral injection. Embodiment 113. The use of a composition comprising an IPO4 polypeptide or a fragment of said IPO4 polypeptide to treat a mammal having a tauopathy. Embodiment 114. An IPO4 polypeptide or a fragment of said IPO4 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. Embodiment 115. An IPO4 polypeptide or a fragment of said IPO4 polypeptide for use in the treatment of a tauopathy. Embodiment 116. The use of a composition comprising nucleic acid encoding an IPO4 polypeptide or a fragment of said IPO4 polypeptide to treat a mammal having a tauopathy. Embodiment 117. Nucleic acid encoding an IPO4 polypeptide or a fragment of said IPO4 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. Embodiment 118. Nucleic acid encoding an IPO4 polypeptide or a fragment of said IPO4 polypeptide for use in the treatment of a tauopathy. Embodiment 119. A method for treating a mammal having a tauopathy, wherein said method comprises administering an IPO11 polypeptide or a fragment of said IPO11 polypeptide to said mammal. Embodiment 120. The method of embodiment 119, wherein said IPO11 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. Embodiment 121. The method of embodiment 120, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, Attorney Docket No.07039-2180WO1 / 2022-349 mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. Embodiment 122. The method of any one of embodiments 119-121, wherein said method comprises identifying said mammal as being in need of said IPO11 polypeptide or said fragment prior to said administering step. Embodiment 123. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering an IPO11 polypeptide or a fragment of said IPO11 polypeptide to said mammal. Embodiment 124. The method of any one of embodiments 119-123, wherein said method comprises administering said IPO11 polypeptide to said mammal. Embodiment 125. The method of any one of embodiments 119-123, wherein said method comprises administering said fragment of said IPO11 polypeptide to said mammal. Embodiment 126. The method of any one of embodiments 123-125, wherein said method comprises identifying said mammal as being in need of said IPO11 polypeptide or said fragment prior to said administering step. Embodiment 127. A method for treating a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO11 polypeptide or a fragment of said IPO11 polypeptide to said mammal, wherein said IPO11 polypeptide or said fragment is expressed by cells in a brain of said mammal. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 128. The method of embodiment 127, wherein said IPO11 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. Embodiment 129. The method of embodiment 128, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. Embodiment 130. The method of any one of embodiments 99-129, wherein said method comprises identifying said mammal as being in need of said nucleic acid prior to said administering step. Embodiment 131. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO11 polypeptide or a fragment of said IPO11 polypeptide to said mammal wherein said IPO11 polypeptide or said fragment is expressed by cells in a brain of said mammal. Embodiment 132. The method of embodiment 131, wherein said method comprises identifying said mammal as being in need of said nucleic acid prior to said administering step. Embodiment 133. The method of any one of embodiments 131-132, wherein said nucleic acid encodes said IPO11 polypeptide. Embodiment 134. The method of any one of embodiments 131-133, wherein said nucleic acid encodes said fragment of said IPO11 polypeptide. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 135. The method of any one of embodiments 131-134, wherein said nucleic acid is in the form of a vector. Embodiment 136. The method of embodiment 135, wherein said vector is an AAV vector. Embodiment 137. The method of embodiment 135, wherein said vector is an expression plasmid. Embodiment 138. The method of any one of embodiments 119-137, wherein said mammal is a human. Embodiment 139. The method of any one of embodiments 119-138, wherein said tauopathy is selected from the group consisting of Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto- nigral degeneration, and primary age-related tauopathy. Embodiment 140. The method of any one of embodiments 119-139, wherein said administering comprises intracerebral injection. Embodiment 141. The use of a composition comprising an IPO4 polypeptide or a fragment of said IPO11 polypeptide to treat a mammal having a tauopathy. Embodiment 142. An IPO11 polypeptide or a fragment of said IPO11 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 143. An IPO11 polypeptide or a fragment of said IPO11 polypeptide for use in the treatment of a tauopathy. Embodiment 144. The use of a composition comprising nucleic acid encoding an IPO11 polypeptide or a fragment of said IPO11 polypeptide to treat a mammal having a tauopathy. Embodiment 145. Nucleic acid encoding an IPO11 polypeptide or a fragment of said IPO11 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. Embodiment 146. Nucleic acid encoding an IPO11 polypeptide or a fragment of said IPO11 polypeptide for use in the treatment of a tauopathy. Embodiment 147. A method for treating a mammal having a tauopathy, wherein said method comprises administering an IPO12 polypeptide or a fragment of said IPO12 polypeptide to said mammal. Embodiment 148. The method of embodiment 147, wherein said IPO12 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. Embodiment 149. The method of embodiment 148, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 150. The method of any one of embodiments 147-149, wherein said method comprises identifying said mammal as being in need of said IPO12 polypeptide or said fragment prior to said administering step. Embodiment 151. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering an IPO12 polypeptide or a fragment of said IPO12 polypeptide to said mammal. Embodiment 152. The method of any one of embodiments 147-151, wherein said method comprises administering said IPO12 polypeptide to said mammal. Embodiment 153. The method of any one of embodiments 147-151, wherein said method comprises administering said fragment of said IPO12 polypeptide to said mammal. Embodiment 154. The method of any one of embodiments 151-153, wherein said method comprises identifying said mammal as being in need of said IPO12 polypeptide or said fragment prior to said administering step. Embodiment 155. A method for treating a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO12 polypeptide or a fragment of said IPO12 polypeptide to said mammal, wherein said IPO12 polypeptide or said fragment is expressed by cells in a brain of said mammal. Embodiment 156. The method of embodiment 155, wherein said IPO12 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. Embodiment 157. The method of embodiment 156, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and Attorney Docket No.07039-2180WO1 / 2022-349 balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. Embodiment 158. The method of any one of embodiments 155-157, wherein said method comprises identifying said mammal as being in need of said nucleic acid prior to said administering step. Embodiment 159. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO12 polypeptide or a fragment of said IPO12 polypeptide to said mammal wherein said IPO12 polypeptide or said fragment is expressed by cells in a brain of said mammal. Embodiment 160. The method of embodiment 159, wherein said method comprises identifying said mammal as being in need of said nucleic acid prior to said administering step. Embodiment 161. The method of any one of embodiments 155-160, wherein said nucleic acid encodes said IPO12 polypeptide. Embodiment 162. The method of any one of embodiments 155-161, wherein said nucleic acid encodes said fragment of said IPO12 polypeptide. Embodiment 163. The method of any one of embodiments 155-162, wherein said nucleic acid is in the form of a vector. Embodiment 164. The method of embodiment 163, wherein said vector is an AAV vector. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 165. The method of embodiment 163, wherein said vector is an expression plasmid. Embodiment 166. The method of any one of embodiments 147-165, wherein said mammal is a human. Embodiment 167. The method of any one of embodiments 147-166, wherein said tauopathy is selected from the group consisting of Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging-related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto- nigral degeneration, and primary age-related tauopathy. Embodiment 168. The method of any one of embodiments 147-167, wherein said administering comprises intracerebral injection. Embodiment 169. The use of a composition comprising an IPO12 polypeptide or a fragment of said IPO12 polypeptide to treat a mammal having a tauopathy. Embodiment 170. An IPO12 polypeptide or a fragment of said IPO12 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. Embodiment 171. An IPO12 polypeptide or a fragment of said IPO12 polypeptide for use in the treatment of a tauopathy. Embodiment 172. The use of a composition comprising nucleic acid encoding an IPO12 polypeptide or a fragment of said IPO12 polypeptide to treat a mammal having a tauopathy. Attorney Docket No.07039-2180WO1 / 2022-349 Embodiment 173. Nucleic acid encoding an IPO12 polypeptide or a fragment of said IPO12 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. Embodiment 174. Nucleic acid encoding an IPO12 polypeptide or a fragment of said IPO12 polypeptide for use in the treatment of a tauopathy. O^THER E^MBODIMENTS It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

Attorney Docket No.07039-2180WO1 / 2022-349 W^HAT I^S C^LAIMED I^S: 1. A method for treating a mammal having a tauopathy, wherein said method comprises administering an IPO13 polypeptide or a fragment of said IPO13 polypeptide to said mammal. 2. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering an IPO13 polypeptide or a fragment of said IPO13 polypeptide to said mammal. 3. A method for treating a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO13 polypeptide or a fragment of said IPO13 polypeptide to said mammal, wherein said IPO13 polypeptide or said fragment is expressed by cells in a brain of said mammal. 4. The method of any one of claims 1-3, wherein said IPO13 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. 5. The method of claim 4, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. 6. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO13 polypeptide or a fragment of said IPO13 polypeptide to said mammal wherein said IPO13 polypeptide or said fragment is expressed by cells in a brain of said mammal. Attorney Docket No.07039-2180WO1 / 2022-349 7. The method of any one of claims 1-6, wherein said fragment of said IPO13 polypeptide consists of the amino acid sequence set forth in any one of SEQ ID NOs:56-77. 8. The method of any one of claims 3-7, wherein said nucleic acid is in the form of a vector. 9. The method of claim 8, wherein said vector is an AAV vector. 10. The method of claim 8, wherein said vector is an expression plasmid. 11. The method of any one of claims 1-10, wherein said mammal is a human. 12. The method of any one of claims 1-11, wherein said tauopathy is selected from the group consisting of Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging- related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, and primary age-related tauopathy. 13. The method of any one of claims 1-11, wherein said tauopathy is a secondary tauopathy selected from the group consisting of Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies. 14. The method of any one of claims 1-13, wherein said administering comprises intracerebral injection. Attorney Docket No.07039-2180WO1 / 2022-349 15. A method for treating a mammal having a tauopathy, wherein said method comprises administering a karyopherin subunit ?1 (KPNB1) polypeptide or a fragment of said KPNB1 polypeptide to said mammal. 16. A method for reducing aggregation of tubulin associated unit (tau) polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide to said mammal. 17. A method for treating a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide to said mammal, wherein said KPNB1 polypeptide or said fragment is expressed by cells in a brain of said mammal. 18. The method of any one of claims 15-17, wherein said KPNB1 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. 19. The method of claim 18, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. 20. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide to said mammal wherein said KPNB1 polypeptide or said fragment is expressed by cells in a brain of said mammal. Attorney Docket No.07039-2180WO1 / 2022-349 21. The method of any one of claims 15-20, wherein said fragment of said KPNB1 polypeptide consists of the amino acid sequence set forth in any one of SEQ ID NOs:7-25. 22. The method of any one of claims 17-21, wherein said nucleic acid is in the form of a vector. 23. The method of claim 22, wherein said vector is an adeno-associated virus (AAV) vector. 24. The method of claim 22, wherein said vector is an expression plasmid. 25. The method of any one of claims 15-24, wherein said mammal is a human. 26. The method of any one of claims 15-25, wherein said tauopathy is selected from the group consisting of Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging- related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, and primary age-related tauopathy. 27. The method of any one of claims 15-25, wherein said tauopathy is a secondary tauopathy selected from the group consisting of Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies. 28. The method of any one of claims 15-27, wherein said administering comprises intracerebral injection. Attorney Docket No.07039-2180WO1 / 2022-349 29. A method for treating a mammal having a tauopathy, wherein said method comprises administering an importin-3 (IPO3) polypeptide or a fragment of said IPO3 polypeptide to said mammal. 30. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering an IPO3 polypeptide or a fragment of said IPO3 polypeptide to said mammal. 31. A method for treating a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO3 polypeptide or a fragment of said IPO3 polypeptide to said mammal, wherein said IPO3 polypeptide or said fragment is expressed by cells in a brain of said mammal. 32. The method of any one of claims 29-31, wherein said IPO3 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. 33. The method of claim 32, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. 34. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO3 polypeptide or a fragment of said IPO3 polypeptide to said mammal wherein said IPO3 polypeptide or said fragment is expressed by cells in a brain of said mammal. Attorney Docket No.07039-2180WO1 / 2022-349 35. The method of any one of claims 29-34, wherein said fragment of said IPO3 polypeptide consists of the amino acid sequence set forth in any one of SEQ ID NOs:26-55. 36. The method of any one of claims 29-35, wherein said nucleic acid is in the form of a vector. 37. The method of claim 36, wherein said vector is an AAV vector. 38. The method of claim 36, wherein said vector is an expression plasmid. 39. The method of any one of claims 29-38, wherein said mammal is a human. 40. The method of any one of claims 29-39, wherein said tauopathy is selected from the group consisting of Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging- related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, and primary age-related tauopathy. 41. The method of any one of claims 29-39, wherein said tauopathy is a secondary tauopathy selected from the group consisting of Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies. 42. The method of any one of claims 29-41, wherein said administering comprises intracerebral injection. 43. A method for treating a mammal having a tauopathy, wherein said method comprises administering an IPO4 polypeptide or a fragment of said IPO4 polypeptide to said mammal. Attorney Docket No.07039-2180WO1 / 2022-349 44. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering an IPO4 polypeptide or a fragment of said IPO4 polypeptide to said mammal. 45. A method for treating a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO4 polypeptide or a fragment of said IPO4 polypeptide to said mammal, wherein said IPO4 polypeptide or said fragment is expressed by cells in a brain of said mammal. 46. The method of any one of claims 43-45, wherein said IPO4 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. 47. The method of claim 46, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. 48. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO4 polypeptide or a fragment of said IPO4 polypeptide to said mammal wherein said IPO4 polypeptide or said fragment is expressed by cells in a brain of said mammal. 49. The method of any one of claims 43-48, wherein said nucleic acid is in the form of a vector. 50. The method of claim 49, wherein said vector is an AAV vector. Attorney Docket No.07039-2180WO1 / 2022-349 51. The method of claim 49, wherein said vector is an expression plasmid. 52. The method of any one of claims 43-51, wherein said mammal is a human. 53. The method of any one of claims 43-52, wherein said tauopathy is selected from the group consisting of Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging- related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, and primary age-related tauopathy. 54. The method of any one of claims 43-52, wherein said tauopathy is a secondary tauopathy selected from the group consisting of Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies. 55. The method of any one of claims 43-54, wherein said administering comprises intracerebral injection. 56. A method for treating a mammal having a tauopathy, wherein said method comprises administering an IPO11 polypeptide or a fragment of said IPO11 polypeptide to said mammal. 57. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering an IPO11 polypeptide or a fragment of said IPO11 polypeptide to said mammal. Attorney Docket No.07039-2180WO1 / 2022-349 58. A method for treating a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO11 polypeptide or a fragment of said IPO11 polypeptide to said mammal, wherein said IPO11 polypeptide or said fragment is expressed by cells in a brain of said mammal. 59. The method of any one of claims 56-58, wherein said IPO11 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. 60. The method of claim 59, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. 61. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO11 polypeptide or a fragment of said IPO11 polypeptide to said mammal wherein said IPO11 polypeptide or said fragment is expressed by cells in a brain of said mammal. 62. The method of any one of claims 56-61, wherein said nucleic acid is in the form of a vector. 63. The method of claim 62, wherein said vector is an AAV vector. 64. The method of claim 62, wherein said vector is an expression plasmid. 65. The method of any one of claims 56-64, wherein said mammal is a human. Attorney Docket No.07039-2180WO1 / 2022-349 66. The method of any one of claims 56-65, wherein said tauopathy is selected from the group consisting of Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging- related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, and primary age-related tauopathy. 67. The method of any one of claims 56-65, wherein said tauopathy is a secondary tauopathy selected from the group consisting of Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies. 68. The method of any one of claims 56-67, wherein said administering comprises intracerebral injection. 69. A method for treating a mammal having a tauopathy, wherein said method comprises administering an IPO12 polypeptide or a fragment of said IPO12 polypeptide to said mammal. 70. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering an IPO12 polypeptide or a fragment of said IPO12 polypeptide to said mammal. 71. A method for treating a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO12 polypeptide or a fragment of said IPO12 polypeptide to said mammal, wherein said IPO12 polypeptide or said fragment is expressed by cells in a brain of said mammal. Attorney Docket No.07039-2180WO1 / 2022-349 72. The method of any one of claims 69-71, wherein said IPO12 polypeptide or said fragment is effective to reduce a symptom of said tauopathy. 73. The method of claim 72, wherein said symptom is selected from the group consisting of memory impairment, problems with language, disorientation, mood swings, social withdrawal, distrust in others, irritability, aggressiveness, changes in sleeping habits, wandering, changes in personality and social behavior, poor coordination and balance, axial rigidity, frequent falls, disturbed eye movements, muscle stiffness, tremor, spasms, slow and slurred speech, difficulty swallowing, asymmetric motor disturbance, ocular apraxia, psychiatric symptoms, and dementia. 74. A method for reducing aggregation of tau polypeptides in a brain of a mammal having a tauopathy, wherein said method comprises administering nucleic acid encoding an IPO12 polypeptide or a fragment of said IPO12 polypeptide to said mammal wherein said IPO12 polypeptide or said fragment is expressed by cells in a brain of said mammal. 75. The method of any one of claims 69-74, wherein said nucleic acid is in the form of a vector. 76. The method of claim 75, wherein said vector is an AAV vector. 77. The method of claim 75, wherein said vector is an expression plasmid. 78. The method of any one of claims 69-77, wherein said mammal is a human. 79. The method of any one of claims 69-78, wherein said tauopathy is selected from the group consisting of Alzheimer’s disease, frontotemporal dementia, Pick's disease, progressive supranuclear palsy, argyrophilic grain disease, globular glial tauopathy, aging- related tau astrogliopathy, Richardson's syndrome, corticobasal degeneration, dementia pugilistica, chronic traumatic encephalopathy, amyotrophic lateral sclerosis/parkinsonism Attorney Docket No.07039-2180WO1 / 2022-349 dementia complex of Guam, frontotemporal dementia parkinsonism linked to chromosome 17, Down syndrome, postencephalitic parkinsonism, pallido-ponto-nigral degeneration, and primary age-related tauopathy. 80. The method of any one of claims 69-78, wherein said tauopathy is a secondary tauopathy selected from the group consisting of Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies. 81. The method of any one of claims 69-80, wherein said administering comprises intracerebral injection. 82. The use of a composition comprising an IPO13 polypeptide or a fragment of said IPO13 polypeptide, a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide, an IPO3 polypeptide or a fragment of said IPO3 polypeptide, an IPO4 polypeptide or a fragment of said IPO4 polypeptide, an IPO11 polypeptide or a fragment of said IPO11 polypeptide, or an IPO12 polypeptide or a fragment of said IPO12 polypeptide to treat a mammal having a tauopathy. 83. An IPO13 polypeptide or a fragment of said IPO13 polypeptide, a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide, an IPO3 polypeptide or a fragment of said IPO3 polypeptide, an IPO4 polypeptide or a fragment of said IPO4 polypeptide, an IPO11 polypeptide or a fragment of said IPO11 polypeptide, or an IPO12 polypeptide or a fragment of said IPO12 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. 84. An IPO13 polypeptide or a fragment of said IPO13 polypeptide, a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide, an IPO3 polypeptide or a fragment of said IPO3 polypeptide, an IPO4 polypeptide or a fragment of said IPO4 polypeptide, an IPO11 polypeptide or a fragment of said IPO11 polypeptide, or an IPO12 polypeptide or a fragment of said IPO12 polypeptide for use in the treatment of a tauopathy. Attorney Docket No.07039-2180WO1 / 2022-349 85. The use of a composition comprising nucleic acid encoding an IPO13 polypeptide or a fragment of said IPO13 polypeptide, a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide, an IPO3 polypeptide or a fragment of said IPO3 polypeptide, an IPO4 polypeptide or a fragment of said IPO4 polypeptide, an IPO11 polypeptide or a fragment of said IPO11 polypeptide, or an IPO12 polypeptide or a fragment of said IPO12 polypeptide to treat a mammal having a tauopathy. 86. Nucleic acid encoding an IPO13 polypeptide or a fragment of said IPO13 polypeptide, a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide, an IPO3 polypeptide or a fragment of said IPO3 polypeptide, an IPO4 polypeptide or a fragment of said IPO4 polypeptide, an IPO11 polypeptide or a fragment of said IPO11 polypeptide, or an IPO12 polypeptide or a fragment of said IPO12 polypeptide for use in the preparation of a medicament to treat a mammal having a tauopathy. 87. Nucleic acid encoding an IPO13 polypeptide or a fragment of said IPO13 polypeptide, a KPNB1 polypeptide or a fragment of said KPNB1 polypeptide, an IPO3 polypeptide or a fragment of said IPO3 polypeptide, an IPO4 polypeptide or a fragment of said IPO4 polypeptide, an IPO11 polypeptide or a fragment of said IPO11 polypeptide, or an IPO12 polypeptide or a fragment of said IPO12 polypeptide for use in the treatment of a tauopathy.