RAMP3 is an accessory protein that modulates G-protein coupled receptor function by facilitating plasma membrane transport and altering ligand specificity. It forms heteromeric receptor complexes with calcitonin receptor-like receptor (CALCRL) to create adrenomedullin and intermedin receptors, and with calcitonin receptor (CALCR) to form amylin receptor 3 1. The stability and signaling output of these complexes are dynamically regulated by agonist binding; for example, human calcitonin and salmon calcitonin agonists promote dissociation of the RAMP3–CALCR complex, whereas different ligands stabilize RAMP3–CALCRL complexes 1. RAMP3 also interacts with estrogen receptor GPER1 to support cardioprotective signaling by reducing cardiac hypertrophy and perivascular fibrosis. Recent evidence indicates that the adrenomedullin-2/RAMP3 pathway promotes tissue-protective innate lymphoid cell responses and limits intestinal inflammation, with altered CALCRL and RAMP3 expression observed in inflammatory bowel disease 2. RAMP3 genetic variants associate with age-related changes in body composition and increased fracture risk in elderly women 3. Clinically, amylin receptor agonists such as pramlintide represent established diabetes therapeutics that target the RAMP3-containing amylin receptor 3 complex.