HLA-DMA is a major histocompatibility complex class II molecule that plays a critical role in antigen presentation by catalyzing the release of the 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. This peptide-loading function occurs in endosomal compartments and is modulated by HLA-DO, particularly in B cells 2. HLA-DMA expression is regulated through conserved S-X-Y regulatory regions requiring class II-specific transcription factors RFX and CIITA 3. Clinically, HLA-DMA has emerged as a significant biomarker in cancer immunotherapy. In lung adenocarcinoma, decreased HLA-DMA expression correlates with poor prognosis and reduced immune infiltration, with higher expression associated with improved survival and enhanced immunotherapy response 4. In ER-negative breast cancer, HLA-DMA expression, when combined with HLA-DRA and Notch genes, synergistically predicts immune checkpoint blockade efficacy and recurrence risk through effects on T cell infiltration 5. Additionally, HLA-DMA is among key genes identified in machine learning models for sepsis identification 6. However, HLA-DMA polymorphisms do not appear to influence rheumatoid arthritis or sarcoidosis susceptibility independently 78.