Adhesion G protein-coupled receptor A2 (GPR124) (ADGRA2)

Adhesion G protein-coupled receptor A2 (ADGRA2), commonly known as GPR124, is a member of the adhesion family of G protein-coupled receptors that plays a critical role in central nervous system (CNS) angiogenesis and the formation of the blood-brain barrier (BBB) [UniProt: Q96P11]. It functions as an essential co-receptor for Wnt7a and Wnt7b ligands, interacting with the GPI-anchored protein Reck to selectively activate Wnt/beta-catenin signaling in CNS endothelial cells [PubMed: 28803732]. This signaling pathway is vital for the proper development of brain vasculature and the maintenance of tight junctions that constitute the BBB [PubMed: 20826365]. In pathological contexts, GPR124 is often upregulated in the vasculature of various tumors, including glioblastomas, where it was originally identified as Tumor Endothelial Marker 5 (TEM5) [PubMed: 11053444]. Its role in promoting vascular stability and BBB integrity makes it a significant therapeutic target for treating ischemic stroke, where restoring BBB function can reduce edema and neuronal damage [PubMed: 30305453]. While no clinical drugs currently target GPR124, research is focused on developing agonists to repair the BBB or antagonists to inhibit tumor-associated angiogenesis [PubMed: 31216451].

Other names

GPR124Tumor endothelial marker 5TEM5Adhesion G protein-coupled receptor A2G protein-coupled receptor 124

Acts as a co-receptor for Wnt7a and Wnt7b ligands, working with Reck to activate the Wnt/beta-catenin signaling pathway specifically in CNS endothelial cells.