Endoplasmic Reticulum Aminopeptidase 1 beyond Antigenic Peptide-Processing Enzyme in the Endoplasmic Reticulum

Endoplasmic reticulum aminopeptidase 1 (ERAP1) is well known as a processing enzyme of antigenic peptides, which are presented to major histocompatibility complex (MHC) class I molecules in the lumen of endoplasmic reticulum. Besides antigen processing, ERAP1 performs multiple functions in various cells depending on its intracellular and extracellular localization. Of note is the secretion of ERAP1 into the extracellular milieu in response to inflammatory stimuli, which further activates immune cells including macrophages and natural killer cells. Furthermore, secreted ERAP1 enhances the expression of pro-inflammatory cytokines like tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6. Such findings indicate that ERAP1 plays a significant role in the field of innate and acquired immunity. This review summarizes the functional analyses of ERAP1 that support our current understanding of its role as more than an antigenic peptide-processing enzyme, specifically emphasizing on its secretory form.