Adhesion G protein-coupled receptors (aGPCRs) are one of the five main families in the GPCR superfamily. They act as a molecular switch that regulate many physiological processes, including brain development, ion–water homeostasis, inflammation and cell-fate determination¹.

One member of the aGPCRs family is the orphan receptor GPR97 (also known as ADGRG3). GPR97 consist of seven-transmembrane domain and a GPCR-Autoproteolysis INducing (GAIN) domain. Auto-cleavage via the GAIN domain produces two subunits: the α-subunit (N-terminal fragment (NTF)) and the β-subunit (C-terminal fragment) that remain non-covalently associated at the cell surface².

GPR97 is mainly expressed in immune cells such as neutrophils, eosinophils, and mast cells. Activation of GPR97 results in reduction in cAMP levels in combination with an increase in downstream effectors of Gβγ, such as SRE and NF-κB3. GPR97 was found to regulate B-cell development in mice and antimicrobial activity in human granulocytes³. In addition, studies have shown that GPR97 is involved in macrophage inflammation in high fat diet–induced obesity in mice⁴.