MEAF6 (MYST/Esa1 associated factor 6) is a non-catalytic scaffolding protein that functions as a core component of multiple histone acetyltransferase complexes. MEAF6 associates with HBO1 (KAT7) to form complexes that specifically mediate acetylation of histone H3 at lysine 14 (H3K14ac) 1, and serves as a component of the NuA4 and MOZ/MORF histone acetyltransferase complexes [UniProt database]. As a scaffold protein, MEAF6 critically modulates substrate specificity; when assembled into the KAT6A four-protein complex with BRPF1 and ING proteins, MEAF6 alters KAT6A's substrate preference by approximately 1000-fold to favor H3K23 acetylation over H3K14 2. These histone modifications regulate transcriptional activation, DNA replication, and DNA repair processes 1. MEAF6 dysfunction is implicated in multiple diseases: alternative splicing of MEAF6 (MEAF6-1) promotes neuroendocrine prostate cancer progression through increased cell proliferation and invasion 3. MEAF6-mediated histone H3 acetylation drives IL-6 expression in bortezomib-resistant multiple myeloma, and miR-197-3p targeting of MEAF6 restores drug sensitivity 4. Additionally, MEAF6-PHF1 gene fusions occur recurrently in endometrial stromal sarcomas and ossifying fibromyxoid tumors, linking MEAF6 to epigenetic transformation in soft tissue neoplasms 56.