Regulator of G-protein signaling 5 (RGS5)

Regulator of G-protein signaling 5 (RGS5) is a specialized GTPase-activating protein (GAP) belonging to the R4 subfamily of RGS proteins. It primarily functions to terminate signaling from G protein-coupled receptors (GPCRs) by accelerating the intrinsic GTPase activity of G-alpha-i/o and G-alpha-q subunits (UniProt: O15539). RGS5 is highly expressed in vascular smooth muscle cells and pericytes, making it a critical modulator of vascular tone and structural remodeling (PubMed: 12065320). In oncology, RGS5 is recognized as a marker for activated tumor pericytes; its overexpression is linked to the development of abnormal, leaky tumor vasculature, while its downregulation can lead to "vessel normalization," improving drug delivery and reducing metastasis (PubMed: 21670306). Beyond cancer, RGS5 is implicated in cardiovascular pathologies such as hypertension and atherosclerosis due to its role in regulating Angiotensin II and Endothelin-1 signaling. Although no FDA-approved drugs currently target RGS5, experimental small molecules like CCG-50014 are being explored as tools to inhibit its activity in various disease models (PubMed: 22122378).

Other names

RGS5Regulator of G protein signaling 5

RGS5 acts as a GTPase-activating protein (GAP) for G-alpha subunits, specifically the Gi/o and Gq families, accelerating the hydrolysis of GTP to GDP to terminate GPCR-mediated signaling.