MED20 is a component of the Mediator complex, a coactivator essential for RNA polymerase II-dependent transcription that bridges gene-specific regulatory proteins to the basal transcription machinery 1. MED20 functions as a scaffold organizing early adipogenic complexes by bridging C/EBPβ and RNA polymerase II to promote PPARγ transcription 1. In the peripheral nervous system, MED20 regulates myelination by suppressing ferroptosis in Schwann cells through a DDB1-UHRF1-BACH1-Hmox1 transcriptional regulatory axis 2. Critically, MED20 acts as a negative regulator of FASN transcription in adipocytes; its loss increases fatty acid synthesis, elevates ROS production, and induces adipocyte necroptosis leading to lipodystrophy 3. Pathogenic variants in MED20 are associated with neurodevelopmental and neurodegenerative phenotypes collectively termed "MEDopathies," characterized by global developmental delay, intellectual disability, hypotonia, and epilepsy 4. MED20 expression is significantly elevated in osteosarcoma and hepatocellular carcinoma, correlating with poor prognosis and immune infiltration patterns [PMID:24101134; 57]. Recent evidence identifies MED20 as a diagnostic biomarker for endometriosis based on lipid metabolism alterations 6. Understanding MED20's tissue-specific roles may enable novel therapeutic strategies targeting metabolic, neurological, and malignant diseases.