CHAF1A (chr19 assembly factor 1 subunit A) functions as a histone chaperone that assembles histone octamers onto DNA during replication and repair as part of the CAF-1 complex 1. Beyond its canonical chr19 assembly role, CHAF1A exhibits diverse regulatory functions across multiple cellular processes. In cancer contexts, CHAF1A acts as an oncogene that blocks neuronal differentiation and promotes aggressive phenotypes in neuroblastoma by upregulating polyamine metabolism and maintaining dedifferentiated states 23. The protein also enhances DNA damage tolerance by recruiting E3 ubiquitin ligase RAD18 to stalled replication forks, facilitating PCNA monoubiquitination and translesion DNA synthesis pathway activation 1. In viral infections, CHAF1A plays contrasting roles: it silences unintegrated HIV-1 DNAs early in infection through H3K9 trimethylation pathways 4, while its stability is regulated by competing ubiquitination and O-GlcNAcylation modifications that control HIV-1 latency 5. Clinically, CHAF1A expression serves as both a prognostic biomarker and therapeutic target, with high expression correlating with poor outcomes in neuroblastoma but favorable immunotherapy responses in gastric cancer 67. Age-related accumulation of CHAF1A in CD4+ T cells correlates with deeper HIV-1 reservoirs, suggesting age-stratified therapeutic implications 5.