PT - JOURNAL ARTICLE AU - Harrison J. McNabb AU - Qian Zhang AU - Benita Sjögren TI - <strong>Emerging roles for Regulator of G Protein Signaling 2 in (patho)physiology</strong> AID - 10.1124/molpharm.120.000111 DP - 2020 Jan 01 TA - Molecular Pharmacology PG - MOLPHARM-MR-2020-000111 4099 - http://molpharm.aspetjournals.org/content/early/2020/09/23/molpharm.120.000111.short 4100 - http://molpharm.aspetjournals.org/content/early/2020/09/23/molpharm.120.000111.full AB - Since their discovery in the mid-1990's, Regulator of G protein Signaling (RGS) proteins have emerged as key regulators of signaling through G Protein-Coupled Receptors (GPCRs). Among the over 20 known RGS proteins, RGS2 has received increasing interest as a potential therapeutic drug target with broad clinical implications. RGS2 is a member of the R4 subfamily of RGS proteins and is unique in that it is selective for Gαq. Despite only having an RGS domain, responsible for the canonical GTPase Activating Protein (GAP) activity, RGS2 can regulate additional processes, such as protein synthesis and adenylate cyclase activity, through protein-protein interactions. Here we provide an update of the current knowledge of RGS2 function as it relates to molecular mechanisms of regulation as well as its potential role in regulating a number of physiological systems and pathologies, including cardiovascular disease and central nervous system disorders, as well as various forms of cancer. Significance Statement RGS proteins represent an exciting class of novel drug targets. RGS2, in particular, could have broad clinical importance. As more details are emerging on the regulation of RGS2 in various physiological systems, the utility of this small protein in therapeutic development is increasing.