ADGRA2 (GPR124, Tumor endothelial marker 5) is a G protein-coupled receptor that is involved in regulating cell adhesion, angiogenesis, polarity acquisition during wound healing and maintenance of the blood-brain barrier in the central nervous system. This receptor contains a leucine rich repeat (LRR), an immunoglobulin (Ig) domain, and a hormone-binding domain (HBD). The Ig domain shows similarities to motilin and titin, while the LRR domain shows similarities to LRIG1 and SLIT1-2. GPR124 can enhance WNT signaling via WNT7, and inactivation has been shown to produce defects in angiogenesis in the forebrain and ventral spinal cord. It is upregulated in the vasculature of some tumors where it likely plays a role in tumor angiogenesis. In immunohistochemistry, this receptor has membranous positivity in the vasculature of the developing liver and brain during embryogenesis. In normal and diseased tissue in adults, it highlights vascular proliferative processes (such as in granulation tissue, pyogenic granulomas and Kaposi's sarcomas) and is present on proliferating endothelial cells. It also has some limited positivity in the central nervous system. References: J Biol Chem. 2017 Jul 21;292(29):12178-12191, PMID: 28600358; Dev Cell. 2014 Oct 27;31(2):248-56, PMID: 25373781; Br J Pharmacol. 2017 Dec;174(24):4547-4563, PMID: 28244067