RGS18 is a member of R4 subfamily of RGS family, a diverse group of multifunctional proteins that regulate cellular signalling events downstream of G-protein coupled receptors (GPCRs) []. Signaling is initiated when GPCRs bind to their ligands, triggering the replacement of GDP bound to the G-alpha subunits of heterotrimeric G proteins with GTP. RGSs inhibit signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. This activity defines them as GTPase activating proteins (GAPs).RGS18 is expressed predominantly in osteoclasts where it acts as a negative regulator of the acidosis-induced osteoclastogenic OGR1/NFAT signaling pathway. RANKL (receptor activator of nuclear factor B ligand) stimulates osteoclastogenesis by inhibiting expression of RGS18 []. RGS18 is also highly expressed in megakaryocytes, platelet, and leukocyte cell lines [, ].
