G protein-coupled receptor 15 (GPR15)

G protein-coupled receptor 15 (GPR15) is a member of the class A orphan GPCR family encoded by the GPR15 gene on chromosome 3q11.2-q13.1 in humans. It is mainly expressed on T cells (especially those trafficked to the colon), endothelial cells, and several epithelial and immune cell types. GPR15 mediates cell signaling involved in T cell chemotaxis to the gut, immune regulation, angiogenesis, and cytoprotection of endothelial cells. It acts as a co-receptor for HIV-1 and HIV-2, enabling viral entry into susceptible cells. GPR15 is implicated in the pathogenesis of inflammatory bowel diseases, chronic inflammatory disorders, certain cancers, and viral infections. Its unique ligand is C10orf99 (AP-57, sometimes called GPR15L). GPR15 is under investigation as a potential therapeutic target in inflammation, autoimmune diseases, and cancer, although no approved drugs directly target it to date.

Other names

BOBHGMWhGPR15GPR15L (note: GPR15L is also used for its ligand C10orf99/AP-57)

Ligand-induced activation recruits G proteins, leading to intracellular signaling (ERK activation, chemotactic responses, etc.). Acts as HIV-1 and HIV-2 co-receptor facilitating entry of these viruses into target cells