PTH1R (parathyroid receptor1, also called PTHR1) is an 85 95 kDa member of the Gprotein coupled receptor family 2 that is a critical receptor regulating Ca++ homeostasis [1 - 5]. The human PTH1R cDNA encodes 593 amino acids (aa) including a 26 aa signal sequence and a long extracellular domain (aa 27 - 189) that contains the PTH (parathyroid hormone) and PTHrP (PTH-related protein) docking site (aa 173 - 189), followed by seven transmembrane domains within the C terminal 404 aa [2 - 4]. Within the N terminal ECD, human PTH1R shares 87%, 88%, 96%, 94% and 93% aa identity with mouse, rat, canine, bovine and porcine PTH1R, respectively. PTH of other mammals will bind and stimulate human PTH1R, although with differing affinities . PTH1R is mainly expressed in bone and kidney, but is also present on hepatocytes, smooth muscle cells, and in other tissues where PTH and PTHrP are found [1 3, 5, 6]. Through PTH1R on osteoblasts, PTH promotes differentiation of osteoclasts, which in turn promote release of Ca++ from bone [1, 5]. PTH1R on osteocytes, however, allows PTH to promote bone formation . In renal epithelium, it promotes conversion of Vitamin D to its active form, lowers Ca++ excretion and increases phosphate excretion [1, 5]. Following PTH binding, PTH1R undergoes a conformation change which activates cAMP, IP3, PKC and Ca++ signaling pathways [1, 8]. PTH1R is then phosphorylated and down-regulated by internalization . Dwarfism in Jansentype metaphyseal chondrodysplasia is associated with PTH1R gain of function, while in Blomstrand chondrodysplasia, PTH1R function is lost [10, 11]. Impaired PTH1R function may be a factor in developmental endochondromas in Ollier disease . Polymorphisms may also be associated with variation in bone mineral density .