Ramp1, or receptor activity modifying protein 1, is a crucial component as it facilitates the localization of the calcitonin-like receptor (CLR) to the plasma membrane. It is involved in the CGRP (calcitonin gene-related peptide) signaling pathway, which plays significant roles in multiple physiological and pathological processes, such as gut mucosal barrier protection, immune regulation, and tissue repair [1-3, 7]. Genetic models, like gene knockout (KO) mouse models, have been pivotal in studying its functions.

In RAMP1-KO mice, liver injury was exacerbated in a hepatic ischemia-reperfusion injury model, with increased hepatocyte apoptosis and inflammation, indicating RAMP1 protects hepatocytes by inhibiting the ERK/YAP pathway [3]. In melanoma, antagonism of the CGRP receptor RAMP1 reduced the exhaustion of tumour-infiltrating leukocytes and decreased tumour growth, suggesting RAMP1 in CD8+ T cells is involved in cancer immunosurveillance [4]. Nociceptor-ablated mice or those lacking epithelial Ramp1 showed increased epithelial stress and susceptibility to colitis, highlighting Ramp1's role in gut barrier protection [1].

In conclusion, Ramp1 plays essential roles in various biological processes including gut protection, immune regulation, and tissue repair. Findings from RAMP1 KO mouse models have significantly advanced our understanding of its functions in diseases such as colitis, endometriosis, and cancer, offering potential therapeutic targets for these conditions [1,2,4].