G protein-coupled receptor 180 (GPR180)

G protein-coupled receptor 180 (GPR180) is a transmembrane protein originally annotated as a seven-transmembrane orphan GPCR, primarily expressed in vascular smooth muscle cells and subsequently identified in diverse tissues including adipose and ocular tissue. GPR180 plays important roles in vascular remodeling, brown/beige adipocyte activation, and glucose metabolism. Importantly, recent structural and functional data show that GPR180 is not a canonical GPCR, lacking the conserved motifs and G-protein signaling features; instead, it acts as a component of the TGFβ receptor complex, mediating SMAD3 phosphorylation and integrating the signaling of its ligand, such as collagen triple helix repeat containing 1 (CTHRC1). GPR180's expression and function are linked to diseases such as congenital microcoria, metabolic disorders, restenosis, and possibly cancer. Although it does not have known approved drugs or antagonists/agonists, its role in these pathways makes it a potential, but still exploratory, therapeutic and biomarker target.

Other names

Intimal thickness-related receptorITRIntegral membrane protein GPR180Intimal thickness related receptor

For potential ligands such as CTHRC1: Modulation of TGFβ signaling and adipocyte activation. No drugs reported with established mechanisms of action targeting GPR180.