Monoclonal antibody 2D7 recognizes the pro-region of Urocortin-2. Urocortins 1, 2 and 3 (Ucn I, Ucn II, and Ucn III), members of the corticotropin releasing factor (CRF)4 family, have diverse bioactivities and participate in the neuroendocrine responses to stress, appetite suppression, immunomodulation, energy and water homeostasis, and cardiovascular function. Their actions are mediated through the 7-transmembrane G-protein coupled receptors CRFR1 and CRFR2. Ucn1 binds to both receptors, whereas Ucn II and Ucn III are specific to CRFR2, widely expressed in the brain, heart, vasculature, and peripheral tissues. Binding of Ucn II to its receptor triggers an intricate signaling cascade via protein kinase C, phosphatidylinositol-3-kinase/Akt and mitogen-activated protein kinase pathways to modulate cytokine expression, cell proliferation, and apoptotic responses. The presence of Ucn II and CRFR2 in the heart and vasculature suggest a potentially important role for Ucn II in the physiology and pathophysiology of the circulation in health and cardiovascular disease. Urocortins exert beneficial effects in experimental cardiovascular disease models and may have therapeutic potential. The sequence of the mature human Ucn II neuropeptide is IVLSLDVPIGLLQILLEQARARAAREQATTNARILARV.