Intracellular antigen processing by ERAP2: Molecular mechanism and roles in health and disease

Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) is an intracellular enzyme localized in the ER that has been shown to play roles in the generation of peptides that serve as ligands for MHC class I (MHC-1) molecules. Although ERAP2 has been primarily described as an accessory and complementary enzyme to the homologous ERAP1, several lines of evidence during the last few years suggest that it can play distinct and important roles in processing antigenic peptides and influencing cellular cytotoxic immune responses. Such emerging evidence has been shaping ERAP2 as a potentially tractable target for regulating select autoimmune and anti-cancer responses for therapeutic purposes. Here, we review the state-of-the-art knowledge on the role of ERAP2 in antigen processing, its structure and molecular mechanism, influence on shaping MHC-I-bound immunopeptidomes and its involvement in disease pathogenesis.