Endoplasmic reticulum aminopeptidase 1 (ERAP1) (ERAP1)

Endoplasmic reticulum aminopeptidase 1 (ERAP1), frequently referred to as ERAAP in murine studies, is a zinc-dependent metalloprotease localized within the lumen of the endoplasmic reticulum (UniProt Q9NZ08). Its primary biological function is the final trimming of N-terminally extended precursor peptides to the optimal length of 8-9 amino acids required for loading onto MHC class I molecules (PubMed: 25637453). This process is critical for the presentation of self and non-self antigens to CD8+ T cells, thereby governing cellular immune responses. Beyond antigen processing, ERAP1 plays a role in regulating blood pressure by inactivating angiotensin II and promoting the shedding of several cytokine receptors, including TNFR1 (PubMed: 11527921). In clinical contexts, ERAP1 is a major genetic risk factor for a group of autoimmune conditions known as MHC-I-opathies, such as ankylosing spondylitis and psoriasis, where specific polymorphisms alter its enzymatic activity and the resulting immunopeptidome (PubMed: 21743467). In oncology, tumors often downregulate ERAP1 to escape immune surveillance, making the restoration or modulation of its activity a target for cancer immunotherapy. Current drug development focuses on small-molecule inhibitors, such as DG013, which aim to shift the peptide repertoire to either suppress autoimmune triggers or enhance the visibility of tumor neoantigens (PubMed: 31434708).

Other names

ERAAPARTS-1A-LAPPILS-APAminopeptidase regulator of autophagy-type 1Adipocyte-derived leucine aminopeptidaseType 1 tumor necrosis factor receptor shedding aminopeptidase regulator

Inhibition of aminopeptidase activity to modulate the repertoire of peptides presented by MHC class I molecules, thereby altering T-cell recognition.