ASF1A is a histone chaperone that facilitates histone deposition, exchange, and removal during nucleosome assembly and disassembly 1. It cooperates with CAF-1 in replication-dependent chr6 assembly and with HIRA in replication-independent chr6 assembly 2. ASF1A recognizes newly synthesized histone H3-H4 dimers bearing specific modifications (H3K9me1K14ac and H4K5K12ac marks) and mediates their nuclear import via importin-4 34. The protein promotes homologous recombination-mediated repair of double-strand breaks by mediating histone replacement and recruiting the MMS22L-TONSL complex and RAD51 5. ASF1A is essential for senescence-associated heterochromatin foci (SAHF) formation and senescence-induced cell cycle exit 6. Clinically, ASF1A expression associates with cancer outcomes. Elevated H3-H4 histone chaperone expression, including ASF1A, correlates with poor hepatocellular carcinoma prognosis and enhanced cell cycle progression 7. Notably, ASF1A loss in tumor cells sensitizes KRAS-mutant lung adenocarcinoma to anti-PD-1 immunotherapy by promoting M1-like macrophage polarization and T-cell activation 8. In contrast, reduced ASF1A expression in healthy aging families associates with familial longevity and healthy aging phenotypes 9, suggesting context-dependent roles in disease and aging.