MED27 encodes mediator complex subunit 27, a critical component of the Mediator complex that serves as a coactivator in RNA polymerase II-mediated transcription 1. The Mediator complex functions as a bridge between gene-specific regulatory proteins and the basal RNA polymerase II transcription machinery, facilitating transcription initiation 2. MED27 is essential for maintaining Mediator complex stability, as mutant variants destabilize the complex and impair its chr9 occupancy, leading to altered chr9 interactions and dysregulation of critical transcription factors involved in neurogenesis and cerebellar development 2. Pathogenic biallelic variants in MED27 cause an autosomal recessive neurodevelopmental disorder characterized by global developmental delay, intellectual disability, cerebellar hypoplasia or atrophy, dystonia, spasticity, and cataracts 13. The clinical phenotype ranges from severe developmental encephalopathy to variable neurodevelopmental disorders, with 100% of patients showing cerebellar atrophy on brain MRI 3. Beyond its neurodevelopmental role, MED27 has been implicated in cancer progression, promoting melanoma and breast cancer growth through various signaling pathways 45. The cerebellum appears particularly vulnerable to MED27 dysfunction, highlighting its critical role in cerebellar development and function.