CGRP (calcitonin gene-related peptide) is a 37-amino-acid neuropeptide produced by tissue-specific splicing of the CALCA gene in primary afferent sensory neurons and central neurons; it signals through a heterodimeric receptor composed of the G-protein-coupled receptor CALCRL and the accessory protein RAMP1, potently dilating cerebral and dermal vasculature, modulating nociceptive transmission, and mediating neuro-inflammatory responses, making it a key target for monoclonal antibodies and small-molecule antagonists in the prevention of migraine and the treatment of cluster headache.