Regulators of G protein signaling (RGS proteins) are a family of highly diverse, multifunctional signaling proteins that share a conserved 120 amino acid domain (RGS domain). RGS domains bind directly to activated G(alpha) subunits and act as GTPase-activating proteins (GAPs) to attenuate and/or modulate hormone and neurotransmitter receptor-initiated signaling by both G(alpha)-GTP and G(beta)(gamma). RGS proteins shorten the lifetime of activated G proteins. Vascular endothelial cells express the RGS protein RGS5, where it correlates with capillary morphogenesis, thus rendering it a candidate gene involved in capillary growth, angiogenesis, and also potentially the pathophysiology of stroke.