HLA-DPA1 encodes the alpha chain of HLA-DP, a major histocompatibility complex (MHC) class II molecule that presents exogenous peptide antigens to CD4+ T cells. The peptide-binding cleft accommodates peptides of 10–30 residues derived from endocytosed antigens processed in the endosomal/lysosomal compartment. HLA-DPA1 partners with HLA-DPB1 to form functional MHC class II heterodimers, which are stabilized by HLA-DM until high-affinity peptides bind; the resulting complex is then displayed on antigen-presenting cells for immune recognition. HLA-DPA1 has been implicated in multiple disease contexts. Common variants in HLA-DPA1/DPB1 are associated with pulmonary arterial hypertension risk, with rs2856830 showing strong correlation with survival—patients homozygous for the C allele had median survival double that of T/T homozygotes 1. In ulcerative colitis, HLA-DPA1*01:03-DPB1*04:01 is a risk haplotype that engages the NK cell receptor NKp44, triggering NK cell activation and intestinal epithelial cell damage 2. HLA-DPA1 expression is downregulated in relapsed acute myeloid leukemia after allogeneic transplantation, enabling immune escape 3. Additionally, HLA-DPA1 polymorphisms influence susceptibility to hepatitis B infection 4 and response to hepatitis B vaccination 5, while downregulation correlates with disease severity in idiopathic pulmonary arterial hypertension 6.