SUPT20H is a component of the SAGA transcriptional coregulator complex located on chromosome 13. As a SAGA-complex member, SUPT20H functions in transcriptional regulation, RNA splicing, and DNA repair processes 1. The gene plays a critical role in p38 MAPK activation and E-cadherin downregulation during gastrulation, and is required for starvation-induced ATG9A trafficking during autophagy [UniProt]. In cancer biology, SUPT20H acts as a negative regulator of B7-H3 expression; loss of SUPT20H constitutively activates p38 MAPK-eIF4E signaling, leading to increased B7-H3 expression and enhanced sensitivity to anti-B7-H3 immunotherapy in tumor models 2. SUPT20H has clinical relevance across multiple diseases: a nonsense variant (c.73A>T, p.Lys25*) shows complete segregation with rheumatoid arthritis in familial cases and is implicated in macro-autophagy and monocyte/macrophage differentiation pathways 3. Additionally, genetic variants associated with SUPT20H expression are significantly associated with aromatase inhibitor discontinuation due to musculoskeletal symptoms in breast cancer patients 4. In gliomas, SUPT20H is part of an autophagy-related gene signature independently associated with patient survival outcomes and tumor immune microenvironment composition 5. These findings establish SUPT20H as a multifunctional regulator with implications for cancer immunotherapy, autoimmune disease, and treatment tolerance.