IPO4 (importin 4) is a nuclear transport receptor mediating selective nuclear import of diverse cargo proteins including histones H3-H4 dimers and monomeric H3.1/H4, RPS3A, TNP2, and VDR 12345. IPO4 recognizes nuclear localization signals (NLS) in substrate proteins and facilitates their translocation through nuclear pore complexes via a Ran-GTP-dependent mechanism, with directional transport conferred by asymmetric Ran-GTP/GDP distribution between cytoplasm and nucleus 12. IPO4 mediates histone H3-H4 import when complexed with ASF1 chaperones and imports monomeric histones as individual units 45. Clinically, IPO4 overexpression associates with poor prognosis in gastric cancer and promotes cell proliferation and migration 6. In cervical cancer, IPO4 mediates CEBPD nuclear import, activating PRKDC-driven DNA damage repair and promoting chemoresistance; IPO4 inhibition enhances cisplatin sensitivity 7. In ovarian cancer, the E3 ligase RNF180 suppresses malignancy by ubiquitinating IPO4 and blocking SOX2 nuclear translocation 8. IPO4 dysfunction impairs MMS22L/CDAN1 complex nuclear import in congenital dyserythropoietic anemia 9. IPO4 also facilitates porcine circovirus replication by interacting with viral capsid protein 10. IPO4 transcription is competitively regulated by ELK1 and GABP 11.