ERAP1ERAP2

ERAP1ERAP2 is a term used to describe the two related endoplasmic reticulum aminopeptidases, ERAP1 and ERAP2, which edit peptide precursors for major histocompatibility complex class I (MHC I) antigen presentation. They belong to the M1 family and can form homo- or heterodimers, trimming peptides within the ER lumen.

Enzymology: Both enzymes trim peptides in a zinc-dependent manner with distinct specificities. ERAP1 tends to shorten longer precursors and can over-trim some peptides, while ERAP2 has more selective activity. Together they can generate optimal 8–9 amino acid peptides for loading onto MHC I, with activity influenced by peptide length, sequence, and ER conditions. Their cooperation may occur when formed as a complex.

Biological role: By shaping the peptide repertoire, ERAP1 and ERAP2 influence which peptides are presented to CD8+ T cells, affecting immune surveillance, tolerance, and responses to infection or malignancy.

Genetics and expression: ERAP1 and ERAP2 genes are located on chromosome 5; expression varies by tissue and activation state. Polymorphisms can alter enzyme activity or expression, including variants that reduce or abolish ERAP2 protein in a substantial subset of individuals.

Clinical significance: Variants in ERAP1 and ERAP2 have been linked to autoimmune diseases such as ankylosing spondylitis and Birdshot chorioretinopathy, and to variation in transplant outcomes and infection responses. Because of their central role in antigen presentation, ERAP1/ERAP2 are investigated as targets for immunomodulation and cancer therapy.