Calcitonin receptor (CALCR) is a transmembrane G-protein coupled protein that is a high-affinity receptor for calcitonin. It is involved in maintaining calcium homeostasis and regulating osteoclast-mediated bone resorption. This receptor is expressed during development and is involved in morphogenesis. In addition to binding calcitonin, CALCR can complex with RAMP3 (receptor activity modifying protein) to bind amylin, which regulates pancreatic islet function and is involved in Type II diabetes. Polymorphisms in the gene are associated with susceptibility to osteoporosis, and different alternatively spliced protein isoforms may regulate biologic responses to calcitonin. Furthermore, loss of functional CALCR through somatic mutation in glioblastoma is associated with an aggressive phenotype and poor prognosis. In immunohistochemistry, CALCR has membranous positivity on neurons in the hypothalamus, in renal tubules, osteoclasts, the testis and kidney. References: J Clin Invest. 1992;90(5):1726-1735. doi: 10.1172/JCI116046; J Clin Invest. 1995;95(6):2680-2691. doi: 10.1172/JCI117970; Clin Cases Miner Bone Metab. 2007;4(2):117-122. PMID: 22461211; vMol Cell Proteomics. 2014;13(2):397-406. doi: 10.1074/mcp.M113.035600; The Journal of Cell Biology. 2004. 164 (4): 509–14, PMID: 14970190; Clin Cancer Res. 2018 Mar 15;24(6):1448-1458, PMID: 29263181;