KPNA6 (karyopherin subunit alpha 6) functions as a nuclear import receptor that recognizes nuclear localization signals (NLS) on cargo proteins and facilitates their translocation into the nucleus. KPNA6 directly interacts with proteins containing NLS motifs and works with KPNB1 to transport cargo through nuclear pore complexes in a Ran-GTP dependent manner 1. The protein plays critical roles in cellular homeostasis by mediating nuclear import of key transcription factors, including HNF1A (where mutations disrupting KPNA6 interaction cause MODY diabetes) 1 and Keap1 (which regulates the antioxidant response by controlling Nrf2 signaling) 2. KPNA6 is also essential for viral replication, serving as a cofactor for ANP32A/B in supporting influenza virus polymerase activity 3 and being required for optimal replication of PRRSV and Zika virus through stabilization mechanisms 4. Additionally, KPNA6 facilitates nuclear import of viral proteins like prototype foamy virus Bel1 transactivator 5 and promotes white adipose tissue browning by enabling IRF4 nuclear translocation 6. The protein's expression and stability are regulated during viral infections, with viruses blocking its proteasomal degradation to maintain elevated levels necessary for replication 4.