SUPT6H is a highly conserved histone chaperone and transcription elongation factor that plays multifaceted roles in gene regulation. As a histone H3-H4 chaperone, SUPT6H facilitates RNA polymerase II (RNAPII) elongation by binding to the phosphorylated C-terminal domain (CTD) of RNAPII and opening the RNA clamp formed by DSIF, thereby enabling pause release and productive transcription 1. SUPT6H functions as part of a regulatory complex with IWS1 that coordinates transcription elongation with mRNA processing and export by recruiting export factors and histone-modifying enzymes like SETD2, ensuring H3K36 methylation during active transcription 2. Beyond elongation, SUPT6H regulates epigenetic remodeling through interaction with KDM6A to erase repressive H3K27me3 marks and maintains ERα-driven transcription in breast cancer cells through histone H2B monoubiquitination regulation 3. Clinically, SUPT6H emerges as a prognostic factor in breast cancer, with protein levels decreasing with malignancy and correlating with cellular differentiation 3. Additionally, SUPT6H has been identified as a platinum-resistance-related gene in ovarian cancer, contributing to a predictive signature for chemotherapy response 4. Recent evidence suggests SUPT6H protects cardiomyocytes from angiotensin II-induced hypertrophy through a miR-423-5p regulatory pathway 5.