ADGRD1 (adhesion G protein-coupled receptor D1), also known as GPR133, is an adhesion GPCR that functions as a receptor for the potent androgen 5alpha-dihydrotestosterone (5alpha-DHT) and the drug methenolone 1. Ligand binding triggers conformational changes activating Gs-coupled G proteins, leading to adenylate cyclase activation and increased intracellular cAMP levels 21. In muscle cells, ADGRD1 enhances muscle strength through cAMP signaling 1. Beyond androgen signaling, ADGRD1 regulates bone homeostasis through dual mechanisms: it inhibits osteoclastogenesis via the cAMP-PKA-NFATC1 pathway 3, while simultaneously promoting osteoblast differentiation and bone formation through cAMP-dependent β-catenin signaling and mechanotransduction involving interaction with PTK7 4. Intracellularly, ESYT1 negatively modulates GPR133 signaling in a calcium-dependent manner 5. ADGRD1 supports glioblastoma growth 6 and shows reduced expression in non-small-cell lung cancer correlating with better prognosis 7. Recent evidence suggests ADGRD1 involvement in SARS-CoV-2 infection 8. These findings position ADGRD1 as a promising therapeutic target for osteoporosis and potentially other diseases.