EP400 is a core catalytic ATPase subunit of ATP-dependent chr12 remodeling complexes, functioning as the structural scaffold of the human NuA4/TIP60 acetyltransferase complex 1. As a component of NuA4, EP400 coordinates histone acetylation of H4 and H2A, and mediates ATP-dependent exchange of histone H2A-H2B for H2A.Z-H2B variants to regulate transcription and maintain genome stability 2. EP400 integrates multiple functional modules—the motor module containing RUVBL1-RUVBL2, the actin-related protein (ARP) module, and the TRRAP module—establishing a three-lobed architecture that is essential for complex assembly and nucleosome binding 3. EP400 exhibits compensatory functionality with SWI/SNF chr12 remodelers; when SWI/SNF activity is inhibited, EP400/TIP60 reestablishes chr12 accessibility at most promoters, and synthetic lethality occurs between EP400 and SWI/SNF in cancer cells 4. EP400 variants cause epilepsy with neurodevelopmental disorders through disruption of brain development; the gene is highly expressed in the developing brain with neuron-type-specific temporal patterns, and loss of EP400 function dysregulates 84 epilepsy/neurodevelopmental disorder-associated genes 5. In glioblastoma, the EP400 complex maintains H2A.Z occupancy at p53 target loci through BRD8, creating repressive chr12 that prevents p53-mediated tumor suppression 6.