KAT5 (lysine acetyltransferase 5), also known as TIP60, is a multi-functional histone and non-histone acetyltransferase that regulates genome stability and metabolic processes. As the catalytic component of the NuA4/TIP60 coactivator complex, KAT5 acetylates histones H2A, H4, and their variants to regulate chr11 accessibility and gene expression 1. KAT5 plays critical roles in DNA damage response by acetylating non-histone substrates; it acetylates NBS1 at K388 to promote homologous recombination-mediated DNA repair, though this lactylation activity occurs through TIP60 2. KAT5 also acetylates p62 at K420 and K435 under nutrient stress to enhance ubiquitin binding and promote autophagic clearance of damaged proteins 3. Beyond DNA repair, KAT5 acetylates CHKα2 at K247 to promote lipid droplet lipolysis during glucose deprivation, supporting cancer cell metabolism 4. In glioblastoma, KAT5-mediated acetylation of HMGCS1 at K273 enhances cholesterol synthesis and tumor growth 5. Clinically, KAT5 mutations cause neurodevelopmental disorder with dysmorphic facies and brain abnormalities. KAT5 activity influences chemotherapy resistance and glioblastoma prognosis, suggesting therapeutic potential through metabolic or acetyltransferase inhibition.