MED31 is a highly conserved subunit of the Mediator complex that serves as a critical transcriptional coactivator for RNA polymerase II-dependent gene expression 1. As part of the core Mediator complex, MED31 functions as a bridge between gene-specific regulatory proteins and the basal transcription machinery, with structural studies revealing it forms specific interactions with the RNA polymerase II C-terminal domain through its knob domain 1. MED31 plays essential roles in stem cell maintenance and differentiation, as knockdown reduces human mesenchymal stem cell self-renewal and impairs adipogenesis 2. The protein undergoes post-translational regulation through ubiquitination, which can be enhanced by cytoplasmic proteins like Elmo1, leading to altered subcellular localization and selective regulation of cytokine genes including Il10 and Il33 3. MED31 has significant clinical relevance, functioning as a tumor suppressor target in osteosarcoma where it is regulated by microRNA-1 and influences MET proto-oncogene signaling 4. Additionally, MED31 DNA methylation is altered by prenatal methylmercury exposure, with changes persisting into childhood and potentially affecting neurodevelopment 56. The gene also shows sex-differential expression patterns in Parkinson's disease and contributes to sleep apnea genetic risk through gene-environment interactions 78.