G protein-coupled receptor 146 (GPR146)

G protein-coupled receptor 146 (GPR146) is a member of the G protein-coupled receptor superfamily, encoded by the GPR146 gene. This membrane protein is characterized by seven transmembrane domains and is primarily involved in the regulation of blood cholesterol levels. GPR146 acts as the receptor for the gut-derived hormone cholesin (C7orf50), inhibiting endogenous cholesterol synthesis upon binding. Experimental disruption of GPR146 in mice and humans leads to reduced serum cholesterol and preserved vascular health, establishing its role in cardiovascular risk. GPR146 is also implicated in C-peptide signaling, with evidence supporting its potential as a target for diabetic microvascular complications and retinopathies through modulation of vascular and retinal cell activity. Preliminary findings indicate a possible role for GPR146 in host antiviral defense. While no approved drugs currently target GPR146, it is considered a promising therapeutic and diagnostic target for lipid metabolism disorders and related diseases, and is the subject of ongoing receptor pharmacology research.

Other names

GPR146G protein-coupled receptor 146GPCR146Q96CH1 (UniProt accession)Cholesin receptor

Modulation of cholesterol synthesis via gut-derived hormone cholesin/C7orf50; Mediation of C-peptide signaling in vascular and metabolic contexts