G-protein coupled receptor 132, (GPR132, G2A) is classified as a member of the proton sensing G-protein coupled receptor (GPCR) subfamily. Like other members of this subfamily, i.e. GPR4, OGR1 (GPR68), and TDAG8 (GPR65), G2A is expressed on the cell surface membrane and contains seven transmembrane domains, similar to serpentine receptors. GPR132 senses changes in extracellular pH, and activation of this proton-sensing receptor by acidosis transduces multiple downstream G protein signaling pathways¹.

GPR132 is expressed in a broad range of immunoregulatory cell types, including macrophages, dendritic cells, neutrophils, mast cells, T and B lymphocytes. It mediates immune cell migration as well as phagocytosis and regulates autoimmunity and lymphocyte homeostasis².

G2A also plays a role in tumor suppression: the tumor microenvironment is acidic due to glycolytic cancer cell metabolism, hypoxia, and deficient blood perfusion and hence, G2A and other proton sensing receptors may be involved in regulation of cancer cell metastasis and proliferation. Small molecule modulators of the pH-sensing GPCRs are being actively developed and evaluated. Research on pH-sensing GPCRs provides important insights into the molecular interaction between the tumor and its acidic microenvironment and may identify new targets for cancer therapy³.