HLA-DMB encodes the beta chain of the non-classical MHC class II protein HLA-DM, which plays a critical role in MHC class II peptide presentation 1. Its primary function is catalyzing the release of class II-associated invariant chain peptide (CLIP) from newly synthesized MHC class II molecules, thereby freeing the peptide binding site for acquisition of antigenic peptides 1. HLA-DMB gene expression is regulated through the conserved S-X-Y regulatory region and requires class II-specific transcription factors RFX and CIITA, similar to classical MHC class II genes 2. Beyond canonical antigen presentation, HLA-DMB exhibits immunomodulatory functions. It restricts human T-cell leukemia virus type-1 (HTLV-1) protein expression by regulating ATG7 acetylation and suppressing autophagosome accumulation, suggesting a role in antiviral defense 3. HLA-DMB polymorphisms associate with multiple diseases: the HLA-DMB*0103 allele shows increased frequency in multiple sclerosis patients 4, and elevated HLA-DMB expression in periodontitis polymorphonuclear neutrophils correlates with disease development and serves as a diagnostic marker 5. However, HLA-DMB polymorphism does not influence rheumatoid arthritis susceptibility 6 or kidney graft rejection outcomes 7, suggesting disease associations are allele- and context-specific rather than universally applicable.