Endoplasmic reticulum aminopeptidase 2 (ERAP2)

Endoplasmic reticulum aminopeptidase 2 (ERAP2) is a zinc-dependent aminopeptidase belonging to the M1 family, expressed in the endoplasmic reticulum (ER) and encoded by the ERAP2 gene in humans. ERAP2 coordinates with ERAP1 to trim N-terminal residues from peptide precursors, generating optimal-length antigenic peptides for MHC class I presentation and controlling the diversity of the immunopeptidome for adaptive immunity. It displays unique substrate selectivity, preferring basic residues, and can efficiently trim even short peptides, often “destroying” potential epitopes. ERAP2 also interacts with ERAP1, potentially forming functional heterodimers that increase trimming efficiency and specificity. Polymorphisms in ERAP2 are linked to differences in immune function, susceptibility to autoimmune diseases, cancer progression, hypertension, and pre-eclampsia. It is emerging as a therapeutic target in cancer immunotherapy and for modulation of inflammatory autoimmunity, though specific clinically approved drugs do not yet exist. Safety and translational research are limited by its absence in rodents and its variable expression in human populations[1][2][3][4].

Other names

ERAP2LRAPL-RAPLeukocyte-derived arginine aminopeptidase

Competitive inhibition of the Zn(II)-dependent catalytic site (mimicking the transition state or substrate) Inhibition of peptide trimming to modulate antigenic peptide production Potential immunomodulation by altering the immunopeptidome and MHC class I presentation