ADGRG2 (adhesion G protein-coupled receptor G2) is an X-linked adhesion GPCR that functions as a steroid hormone receptor essential for male reproductive function. The receptor binds steroid hormones including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate, androstenedione, and deoxycorticosterone 1. ADGRG2 undergoes autoproteolysis to produce α and β subunits, with activation mediated by a tethered agonism mechanism involving the Stachel sequence of the β subunit 2. Upon ligand binding, ADGRG2 couples primarily to Gs proteins to activate adenylate cyclase signaling pathways, though it can also couple to Gq proteins in vitro 1. The receptor is critical for epididymal function and male fertility, working together with CFTR to promote fluid reabsorption within efferent ductules 3. Mutations in ADGRG2 cause congenital bilateral aplasia of the vas deferens (CBAVD), a form of obstructive azoospermia that contributes significantly to male infertility 3. Novel mutations have also been associated with micropenis and other male reproductive abnormalities 4. Genetic testing for ADGRG2 mutations is now recommended in the diagnostic workup of male infertility, as it helps predict the success rate of testicular sperm extraction procedures 3.