RAMP1 (receptor activity modifying protein 1) is a critical accessory protein that modulates G-protein coupled receptor function 1. RAMP1 interacts with calcitonin receptor-like receptor (CALCRL) to form the calcitonin gene-related peptide (CGRP) receptor complex and with calcitonin receptor (CALCR) to constitute the amylin receptor 1 (AMYR1) 12. The protein is essential for CALCRL transport to the plasma membrane, enabling proper receptor localization and signaling 3. Mechanistically, RAMP1-mediated CGRP signaling operates as a neuroimmune axis with context-dependent effects. In tumor immunosurveillance, CGRP-RAMP1 signaling on CD8+ T cells promotes their exhaustion, reducing anti-tumor immunity; RAMP1 antagonism nearly tripled survival in melanoma-bearing mice 4. Conversely, CGRP-RAMP1 signaling on neutrophils and macrophages promotes tissue healing by enhancing efferocytosis and polarizing macrophages toward pro-repair phenotypes 5. In gastric cancer, sensory neuron-derived CGRP via RAMP1 drives tumor progression 6. RAMP1 is also expressed on goblet cells, where CGRP-RAMP1 signaling induces mucus secretion and gut barrier protection 7. Clinically, RAMP1 expression correlates with poor prognosis in melanoma and is elevated in endometriosis lesions 48. CGRP-RAMP1 blockade reduced endometriosis pain and lesion growth 8, while targeting this axis in breast cancer remodeled the immune-excluded tumor microenvironment and enhanced PD-1 immunotherapy efficacy 9.