IPO4 is a nuclear transport receptor that mediates the import of diverse protein substrates into the nucleus, including histones H3 and H4, VDR, and FANCD2. The protein recognizes nuclear localization signals in cargo and facilitates their translocation across the nuclear pore complex through a Ran-GTP–dependent mechanism. IPO4 functions as the primary receptor for the H3-H4 dimer when complexed with histone chaperone ASF1, and also mediates import of monomeric H3.1 and H4 1. Nup98, a key nucleoporin, is essential for IPO4-dependent transport, interacting with IPO4 through FG repeat motifs to enable substrate translocation 2. In cancer contexts, IPO4 contributes to pathological progression. IPO4 is overexpressed in gastric cancer tissues and correlates with poor survival; knockdown impairs cancer cell proliferation and migration 3. In cervical cancer, IPO4 augments nuclear translocation of the transcription factor CEBPD, which upregulates PRKDC and drives chemoresistance to cisplatin; combining IPO4 or PRKDC inhibition (NU7026) with cisplatin enhances chemosensitivity 4. In ovarian cancer, the E3 ubiquitin ligase RNF180 suppresses malignancy by promoting IPO4 degradation and blocking SOX2 nuclear import 5. Beyond cancer, IPO4 is required for normal erythropoiesis; mutations impairing IPO4-CDAN1 interaction cause congenital pure red cell aplasia 6. IPO4 is also hijacked during porcine circovirus infection to facilitate viral replication 7.