Importin subunit alpha-3

KPNA4 encodes importin subunit alpha-3, a 57.9 kDa adapter protein essential for nuclear protein import (UniProt: O00629). It functions by binding substrates containing nuclear localization signals (NLS) and mediating their translocation through the nuclear pore complex in coordination with importin-beta (KPNB1) and the Ran GTPase system. Known cargo substrates include AARS1, MRTFA, and RANBP3 (UniProt: O00629).

KPNA4 is expressed broadly across human tissues with roles in fundamental nucleocytoplasmic transport. The protein has no curated genetic disease associations in UniProt, though nuclear import machinery is implicated in various pathological contexts including viral infection (UniProt: O00629).

In Alzheimer's Disease, KPNA4 is significantly upregulated in post-mortem human brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.42 (Chaparral AD proteomics). This elevation suggests altered nuclear import capacity may be relevant to AD pathology, though the functional consequence of increased KPNA4 expression in neurodegeneration requires further investigation.