CALCA (calcitonin-related peptide alpha) encodes a potent neuropeptide hormone with primary roles in vasodilation and pain signaling. The peptide induces vasodilation across coronary, cerebral, and systemic vasculature through activation of the CALCRL-RAMP1 receptor complex 12, and can also activate the CALCR-RAMP1 (AMYR1) complex 3. CALCA functions as a neurotransmitter/neuromodulator in the central nervous system 4 and elevates platelet cAMP 1. In developmental contexts, CALCA promotes placental angiogenesis by stimulating endothelial cell proliferation, migration, and tube formation, suggesting autocrine/paracrine regulation of fetal vascularization 5. CALCA is highly expressed in nociceptors, particularly in female C-nociceptors involved in pain perception 6. Clinically, CALCA variants associate with multiple pathologies: the CALCA rs3781719 C allele increases chr11 pain risk after cesarean section 7, while genetic variants in the 5' flanking region correlate with essential hypertension susceptibility 8. αCGRP (CALCA product) deficiency aggravates pulmonary fibrosis by promoting alveolar type 2 cell senescence and inflammation 9. These findings highlight CALCA's therapeutic potential for pain management, vascular disorders, and fibrotic diseases.