ADGRA2 (adhesion G protein-coupled receptor A2) is an endothelial receptor that functions as a Wnt7-specific coactivator of canonical Wnt signaling 1. Its primary role is to facilitate delivery of RECK-bound Wnt7a/7b ligands to Frizzled receptors by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 signaling complex 2. Notably, ADGRA2's signaling function operates independently of its GPCR structure, relying instead on its capacity to interact with RECK extracellularly and recruit the Dishevelled scaffolding protein intracellularly 2. In the central nervous system, ADGRA2 mediates Wnt7-dependent endothelial cell sprouting and migration while establishing blood-brain barrier integrity 3. ADGRA2 also binds glycosaminoglycans including heparin and heparan sulfate 4. Clinically, ADGRA2 amplifications are associated with worse neoadjuvant chemotherapy response and poor prognosis in breast cancer patients 5. Genetic variants in ADGRA2 have been linked to bifrontal polymicrogyria with multiple congenital anomalies, suggesting its importance in cortical development 6. Additionally, ADGRA2 is a predicted target for proteolytic cleavage by viral proteases from neuroinvasive viruses, potentially contributing to blood-brain barrier disruption during CNS infections 7.