ADM2 (adrenomedullin 2), also known as intermedin, is a peptide hormone that functions as a cardiovascular and gastrointestinal regulator through interaction with CALCRL-RAMP receptor complexes, particularly CALCRL-RAMP3, activating the cAMP/PKA signaling pathway 1. The protein plays critical roles in vascular function, promoting vasodilation in pregnant uterine arteries and inhibiting vascular calcification in diabetic conditions 21. ADM2 demonstrates significant tissue-protective functions by promoting group 2 innate lymphoid cell (ILC2) responses and limiting intestinal inflammation through amphiregulin production 3. In reproductive biology, ADM2 enhances trophoblast invasion and migration, regulates HLA-G expression under hypoxic conditions, and shows decreased expression in preeclampsia, suggesting involvement in placental pathophysiology 456. The hormone also contributes to innate immune responses in the intestine, with expression regulated by bitter taste receptors and affecting antimicrobial peptide release 7. Clinically, reduced ADM2 levels are associated with type 2 diabetes, preeclampsia, and inflammatory bowel diseases, while therapeutic ADM2 delivery shows promise for treating intestinal inflammation and vascular calcification 316.