KPNA3 encodes karyopherin alpha 3, a nuclear import adapter protein that mediates the transport of cargo proteins containing nuclear localization signals (NLS) into the nucleus 1. The protein functions as part of the classical nuclear import pathway, forming complexes with importin β1 and cargo proteins to facilitate their translocation through nuclear pores 2. KPNA3 demonstrates specificity for certain substrates, including NPAT (required for histone locus body formation) and various viral proteins 2. Beyond its canonical transport role, KPNA3 regulates cellular processes including epithelial-mesenchymal transition in triple-negative breast cancer through TGF-β and AKT signaling pathways 3. The protein also modulates phase separation by preventing aberrant cytoplasmic condensation of substrates like NPAT through steric hindrance mechanisms 2. Clinically, KPNA3 shows significant disease relevance, with genetic variants associated with multiple psychiatric disorders including schizophrenia, major depression, and substance dependencies 456. Additionally, KPNA3 is implicated in cancer progression and chemoresistance, particularly in colorectal cancer where it functions downstream of SIRT1 signaling 7. Mouse studies suggest KPNA3 deficiency enhances reward-seeking behavior, supporting its role in motivational control 8.