ERAP1

Class

ERAP1 (endoplasmic reticulum aminopeptidase 1) inhibitor

Pathway

MHC-I antigen processing/presentation, novel tumor antigen generation

ERAP1, endoplasmic reticulum aminopeptidase 1, is an enzyme that trims longer peptide fragments down to the precise length needed for loading onto MHC class I molecules, the surface proteins that display fragments of a cell's internal proteins to the immune system's CD8+ T cells. This process, called antigen processing and presentation, determines which peptides a cell shows on its surface and therefore which cells the immune system recognizes as normal versus abnormal. Because ERAP1 shapes the final peptide repertoire, inhibiting it changes the mix of peptides displayed, potentially generating new or previously hidden peptide sequences, sometimes called neoantigens, that were not visible before. In cancer, this is of interest because tumor cells often display a limited or tolerogenic peptide set; altering that repertoire may make tumors more visible to T cells and support immunotherapy approaches. ERAP1 activity has also been linked to autoimmune conditions, where certain peptide-trimming patterns are associated with inappropriate immune recognition of self-tissue. Modulating this single enzyme therefore has broad relevance across oncology and immune-mediated disease, since it acts upstream of a fundamental process common to nearly all nucleated cells.