Parathyroid hormone (PTH) is recognized by three different class B GPCRs; PTH1, PTH2, and PTH3, which couple to Gs to stimulate cAMP production. The PTH1 receptor is found in high levels in the kidney and bone, where it binds PTH and PTHrP to regulate Ca2+ homeostasis. The PTH2 receptor, which binds PTH and the neuropeptide tuberoinfundibular peptide 39 (TIP-39) but not PTHrP, has about 50% amino acid sequence identity to the PTH1 receptor. PTH2 is found in the greatest volume in the nervous system and at a very low density in the kidney and bone. The PTH3 receptor, which has been recently discovered in the zebrafish, has 61% amino acid identity to the zebrafish PTH1 receptor and also seems to share its ligand affinity. Studies with the selective PTH2 receptor agonist, TIP-39, and the distribution of the receptor in the superficial dorsal horn of the spinal cord suggest the receptor may play a role in pain perception.