ASF1A is a histone H3-H4 chaperone that facilitates nucleosome assembly and disassembly by mediating histone deposition and exchange. It cooperates with CAF-1 in replication-dependent chr6 assembly and with HIRA in replication-independent assembly, and recognizes newly synthesized histones bearing specific post-translational marks during nuclear import via importin-4. ASF1A also promotes homologous recombination-mediated repair of double-strand breaks by recruiting the MMS22L-TONSL complex and facilitates formation of senescence-associated heterochromatin foci. ASF1A is overexpressed across multiple cancer types including hepatocellular carcinoma, breast cancer, and prostate cancer, where elevated levels correlate with poor prognosis 1. ASF1A inhibition induces p53-dependent senescence and growth arrest in cancer cells with wild-type p53 1, and its deubiquitination by USP52 stabilizes the protein to promote cell cycle progression 2. In KRAS-mutant lung adenocarcinoma, ASF1A loss sensitizes tumors to anti-PD-1 immunotherapy by promoting M1-like macrophage polarization and enhancing T-cell activation 3. In hepatocellular carcinoma patients, a prognostic two-gene model incorporating ASF1A predicts survival outcomes and sensitivity to immune checkpoint therapy 4.