CALCB (calcitonin gene-related peptide beta, CGRP-β) is a neuropeptide hormone that functions primarily as a vasodilator and neuromodulator. It signals through the CALCRL-RAMP1 receptor complex to induce vasodilation across coronary, cerebral, and systemic vasculature 12. The peptide is abundantly expressed in the central nervous system, supporting roles as a neurotransmitter or neuromodulator 3. CALCB plays important roles in immune homeostasis and neuroinflammation. In sensory neurons, JAK1-dependent CALCB expression suppresses group 2 innate lymphoid cell function and allergic airway inflammation 4. Additionally, CALCB has been implicated in skeletal innervation and bone metabolism, with reduced CGRP signaling associated with diabetic peripheral neuropathy-related bone disease 5. Genetically, CALCB variants are significantly associated with migraine susceptibility; genome-wide studies identified CALCB among 123 migraine risk loci, with enrichment in both vascular and central nervous system tissues supporting neurovascular mechanisms of migraine pathophysiology 67. CALCB polymorphisms also associate with adenoid cystic carcinoma susceptibility, with low CALCB expression correlating with increased cancer risk 8. In Ewing sarcoma, CALCB is directly regulated by EWSR1-FLI1 fusion protein and supports tumor growth through RAMP1 signaling, representing a potential therapeutic target 9.