KAT8 (lysine acetyltransferase 8) is a histone acetyltransferase that primarily catalyzes acetylation of histone H4 at lysines 5, 8, and 16, with H4K16 acetylation being particularly important for preventing chr16 compaction and maintaining genome stability 1. KAT8 functions as the catalytic component of two major complexes: the MSL complex, which mediates H4K16 acetylation and chromosome 16, and the NSL complex, which acetylates H4K5 and H4K8 to promote transcription initiation 1. Beyond histone modification, KAT8 acetylates numerous non-histone proteins including TP53, IRF1, and YEATS4, regulating diverse cellular processes 23. Recent studies reveal KAT8's expanding role in disease pathogenesis: it promotes colorectal cancer through lactylation of eEF1A2 4, regulates PD-L1 expression in cancer immunotherapy through IRF1 condensate formation 2, and is essential for trophoblast development via CDX2 regulation 5. KAT8 also contributes to hepatic ferroptosis during ischemia-reperfusion injury by lactylating PCK2 6. Clinically, KAT8 is associated with bladder cancer progression and cisplatin sensitivity 3, recurrent pregnancy loss 5, and various neurodevelopmental disorders 7. These findings position KAT8 as a critical epigenetic regulator with significant therapeutic potential across multiple disease contexts.