MED11 is a core component of the Mediator complex, a multi-subunit coactivator essential for RNA polymerase II-dependent transcription 1. As part of the head module, MED11 participates in bridging gene-specific regulatory proteins to the basal transcription machinery and facilitates pre-initiation complex assembly 1. The protein demonstrates activator-specific requirements for transcriptional activation, with evidence suggesting distinct roles in mediating different transcriptional signals 2. MED11 is also implicated in HIV-1 transcription, where its knockdown significantly impairs viral replication by inhibiting early HIV transcripts 3. Pathogenic variants in MED11 cause neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities (NDDRSB), classified within the broader MEDopathies spectrum 4. Homozygous truncating variants (c.325C>T; p.Arg109Ter) produce catastrophic infantile neurodegeneration characterized by microcephaly, profound neurodevelopmental impairment, exaggerated startle response, myoclonic seizures, and premature death 5. The C-terminal truncation impairs binding to other Mediator subunits, disrupting complex stability 5. Recent findings expand the prenatal phenotypic spectrum to include hydrops fetalis and abnormal limb posturing 6, with neuroradiological features including callosal abnormalities, hypomyelination, and progressive neurodegeneration 4.