Nucleobindin 2 (NUCB2) is a multifunctional protein containing several functional domains and is associated with a wide variety of biological processes such as food intake and energy homeostasis. Nesfatin-1/NucB2, an anorexigenic molecule, is expressed mainly in the hypothalamus, particularly in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). Nesfatin-1/NucB2 is also expressed in the subfornical organ (SFO). Because the SON and PVN are involved in body fluid regulation, nesfatin-1/NucB2 may be involved in dehydration-induced anorexia. NUCB2 plays a well-established role in homeostatic functions associated with food intake and stress integration. Nesfatin-1 is a hypothalamic anorexigenic peptide processed from Nucleobindin 2 (NUCB2). Central and peripheral administration of NUCB2/nesfatin-1 enhances glucose metabolism and insulin release. NUCB2/nesfatin-1 is also localized in pancreatic islets.