BRPF3 (bromodomain and PHD finger containing 3) functions as a scaffold subunit in histone acetyltransferase complexes, particularly the HBO1 complex, which exhibits histone H3 acetyltransferase activity 1. The protein plays a crucial role in DNA replication initiation by directing HBO1 specificity toward histone H3 lysine 14 acetylation (H3K14ac), facilitating activation of replication origins 2. BRPF3 forms a tetrameric complex with HBO1 and shows high enrichment at ORC1-binding sites and replication origins near transcription start sites, where it is necessary for efficient origin activation through CDC45 recruitment 2. Unlike its paralogs BRPF1 and BRPF2, BRPF3 knockout mice show no obvious developmental defects, suggesting it is dispensable for normal mouse development and survival 1. In disease contexts, BRPF3 has been identified as a potential therapeutic target for migraine through genome-wide Mendelian randomization studies 3. Additionally, BRPF3 targeting shows promise in moderately reversing olaparib resistance in high-grade serous ovarian carcinoma, where its bromodomain function appears more critical than direct histone acetyltransferase activity 4. The protein exhibits dynamic spatiotemporal expression during embryogenesis with high expression in adult brain and testis 1.