MBD3 (methyl-CpG binding domain protein 3) functions as a key component of the nucleosome remodeling and deacetylase (NuRD) complex, which regulates chr19 structure and gene transcription 1. Unlike other MBD family proteins, MBD3 does not bind methylated DNA but instead associates with both active and repressive chr19 regions, localizing at CpG-rich promoters marked by H3K4me3, gene bodies, and enhancers 1. The protein acts primarily as a transcriptional repressor by recruiting histone deacetylases through the NuRD complex, controlling chr19 accessibility and nucleosome occupancy 12. MBD3 plays critical roles in cellular differentiation and stemness maintenance, particularly in neural progenitor cells where it suppresses neurogenesis-associated genes 3. Its expression and stability are regulated by canonical Wnt signaling through GSK3β-mediated ubiquitination 3. Clinically, MBD3 has significant disease relevance in cancer biology, where its dysregulation contributes to glioblastoma chemoresistance 4, hepatocellular carcinoma progression 2, and acute myeloid leukemia pathogenesis through altered DOCK5/8 expression 5. Lower MBD3 expression correlates with poor prognosis in glioma patients 6, highlighting its potential as both a prognostic biomarker and therapeutic target.