Calcitonin is a 32 amino acid polypeptide hormone that preserves skeletal integrity and reduces blood calcium levels by decreasing osteoclast activity in bones, calcium and phosphate reabsorption by kidney tubules, and calcium absorption by the intestines. The secretion of Calcitonin from the thyroid is regulated in part by estrogen, which increases Calcitonin mRNA levels. The Calcitonin gene, CALCA, undergoes tissue-specific RNA alternative splicing, resulting in the production of different mRNA transcripts. One transcript encodes procalcitonin and both calcium-lowering processed active polypeptides, Calcitonin, and katacalcin. An alternative transcript of CALCA encodes the precursor for the neuropeptide called Calcitonin gene-related peptide 1, also designated CGRP1 or -CGRP. CGRP is a widely distributed vasodilatory peptide. Calcitonin and katacalcin are produced primarily in the thyroid, while CGRP is produced in neuronal cells. A second CGRP related gene, CALCB, which is thought to be derived from a gene duplication event, has been identified in mice, rats, and humans. Unlike CALCA, CALCB is not subject to alternative splicing and encodes a single transcript designated CGRP2 or -CGRP. Mature CGRP1 and CGRP2 share significant sequence identity at the protein level differing by only 1-3 amino acid residues, depending on the species.