ERAP1 is an endoplasmic reticulum aminopeptidase that plays a central role in peptide trimming, essential for generating MHC class I-binding peptides 1. The enzyme preferentially processes peptides 9-16 residues long, rapidly converting 13-mers to 9-mers while favoring substrates with hydrophobic C-termini [UniProt]. This peptide trimming shapes the HLA class I peptidome, directly affecting both adaptive and innate immune responses 2. ERAP1 genetic variants are significantly associated with multiple diseases. Specific polymorphisms (rs30187 and rs27524) increase psoriasis susceptibility 3, while ERAP1 expression is frequently altered in tumors, influencing anti-tumor immunity 1. Notably, ERAP1 variants with reduced endopeptidase activity appear protective against ankylosing spondylitis, a strong HLA-B27-associated condition 4. Recent evidence demonstrates that ERAP1 loss disrupts the NKG2A-HLA-E inhibitory checkpoint by altering the HLA-E peptidome, enhancing antitumor immunity and sensitizing tumors to immune checkpoint blockade 5. This suggests ERAP1 inhibition represents a potential therapeutic strategy for both autoimmune diseases and cancer immunotherapy.