RGS5

RGS5 is a protein-coding gene in humans that encodes regulator of G-protein signaling 5, a member of the RGS protein family. RGS proteins act as GTPase-activating proteins for the alpha subunits of heterotrimeric G proteins, accelerating hydrolysis of GTP to GDP and thereby terminating signaling from G protein-coupled receptors.

RGS5 preferentially accelerates GTP hydrolysis by certain G alpha subunits, notably Gαq/11 and Gαi/o, and modulates signaling downstream of a range of GPCRs involved in vascular function, such as endothelin, angiotensin II, norepinephrine, and vasopressin pathways. In cells of the vascular wall, including pericytes and vascular smooth muscle cells, RGS5 helps regulate vascular tone, remodeling, and angiogenesis by limiting excessive GPCR signaling.

Expression of RGS5 is enriched in vascular tissues and in pericytes associated with microvessels. Its transcription can be influenced by developmental cues and pathological conditions, including hypoxia and the tumor microenvironment, where RGS5 is often upregulated in tumor-associated vasculature and used as a pericyte marker.

Clinical and research interest in RGS5 centers on its role in angiogenesis and vascular maturation, with investigation into its potential as a biomarker for vascular health or a therapeutic target in cancer and cardiovascular disease. The protein contains the conserved RGS domain responsible for GAP activity and is part of the broader RGS family that regulates GPCR signaling.