ERAP2 (endoplasmic reticulum aminopeptidase 2) is a metalloaminopeptidase that plays a central role in antigen processing and presentation via MHC class I molecules 12. The enzyme functions by trimming peptides to the optimal length required for presentation on MHC class I molecules, preferentially cleaving basic residues such as arginine and lysine in the endoplasmic reticulum lumen 1. ERAP2 exhibits remarkable genetic polymorphism across human populations, with haplotypes that encode different functional variants 32. These genetic variations have significant disease relevance, as ERAP2 polymorphisms are associated with autoimmune diseases, infectious diseases, and cancers 2. Notably, ERAP2 variants were under positive selection during historical pandemics, including the Black Death, where the rs2549794 variant associated with full-length ERAP2 production provided protection against Yersinia pestis by improving cytokine responses and intracellular bacterial control in macrophages 4. However, these historically protective variants paradoxically increase susceptibility to modern autoimmune diseases, exemplifying evolutionary trade-offs 4. ERAP2 has also been implicated in birdshot chorioretinopathy pathogenesis 5 and identified as a potential therapeutic target for various conditions including intracranial aneurysms 6.