PTH1R is a G-protein-coupled receptor that functions as the primary mediator of parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHLH) signaling 1. Upon ligand binding, PTH1R undergoes conformational changes that activate downstream G-protein signaling, predominantly coupling to G(s) alpha proteins to stimulate adenylate cyclase and increase intracellular cAMP levels 23. PTHLH dissociates from PTH1R more rapidly than PTH, resulting in faster decay of cAMP responses 3. PTH1R regulates bone metabolism by directly activating osteoblasts and indirectly influencing osteoclasts and osteoclast precursors through multiple pathways including Wnt signaling, cAMP/PKA, and RANKL/RANK/OPG cascades 4. In skeletal development, PTHrP-mediated PTH1R activation controls growth plate development pace in chondrocytes 5. Clinically, PTH1R agonists teriparatide and abaloparatide are first-line osteoanabolic agents for osteoporosis, increasing bone mineral density and reducing fracture risk in postmenopausal women 67. Mutations in PTH1R cause rare skeletal dysplasias including Jansen metaphyseal chondrodysplasia and Blomstrand chondrodysplasia, and loss-of-function variants cause primary failure of tooth eruption, with over 50 different PTH1R variants identified in affected patients 8. PTH1R signaling also contributes to cardiovascular homeostasis, with dysregulation implicated in primary hyperparathyroidism-associated cardiovascular disease 9.