Nerves, and the signals that modulate them, play critical roles during wound healing. CGRP (calcitonin gene-related peptide) is one such modulator and is a potential treatment target for chronic wounds, like ulcers. But CGRP doesn’t last long in blood samples, so researchers recently focused on RAMP1 (receptor activity-modifying protein 1), which is part of the CGRP receptor. First, in mouse experiments, they determined that RAMP1 expression was altered during skin wound healing. Then, they used mouse skin fibroblasts (MSFs) to determine the mechanisms at play. Overexpressing RAMP1 in MSFs promoted proliferation by increasing expression of YAP (Yes-associated protein). Subsequent experiments showed that overexpressed RAMP1 increased expression of Gαi3 (inhibitory G protein α subunit 3). While Gαi3 is typically inhibitory, here Gαi3 activated PKA (protein kinase A) through a non-classical pathway. The newly activated PKA elevated the expression of CREB (cAMP response element-binding protein) and activated it. CREB then promoted transcription of the YAP gene, which ultimately increased MSF proliferation. These results demonstrate that RAMP1 overexpression increases MSF proliferation via the Gαi3-PKA-CREB-YAP1 axis. While further studies are needed to confirm this pathway directly in wounds, this axis is a promising potential treatment target for wound healing.