CALCB encodes calcitonin gene-related peptide beta (βCGRP), a neuropeptide hormone that induces vasodilation through the CALCRL-RAMP1 receptor complex, affecting coronary, cerebral, and systemic blood vessels. Its abundant expression in the central nervous system suggests additional neurotransmitter and neuromodulator roles. CALCB operates through G protein-coupled receptor signaling that activates adenylate cyclase and regulates intracellular calcium homeostasis. CACLB has emerged as a therapeutic target in migraine, a condition affecting over a billion individuals worldwide 1. Three monoclonal antibodies targeting the CGRP pathway—eptinezumab, fremanezumab, and galcanezumab—are now approved therapies that block CGRP signaling to reduce migraine frequency. Recent integrative genomic analyses identify CALCB as a migraine-associated locus 2, supporting its role in migraine pathophysiology through neurovascular mechanisms. Beyond migraine, CALCB expression is reduced in pancreatic ductal adenocarcinoma and adenoid cystic carcinoma of the salivary gland, with the latter showing associations between CALCB polymorphisms and disease susceptibility 3. In Ewing sarcoma, CALCB is directly regulated by the EWSR1-FLI1 fusion protein, and targeting the CALCB/RAMP1 axis reduces tumor growth both in vitro and in vivo 4. CALCB also modulates immune homeostasis in respiratory tissues through JAK1-dependent signaling in sensory neurons 5.