Nucleobindin-2 (NUCB2; Prepronesfatin) was first isolated in adipocytes, but is also expressed by gastric mucosa and pancreatic beta cells. This pattern of nucleobindin-2 expression, as well as the presence of nucleobindin-2 within the plasma of rodents and humans, strongly suggests that this compound may act as a circulating regulatory factor. NUCB2 can be cleaved into three polypeptides: nesfatin-1, nesfatin-2, and nesfatin-3. Anorexigenic effects have been described for nesfatin-1 that plays an important role in hypothalamic pathways regulating food intake and energy homeostasis and acting in a leptin-independent manner. Nesfatin-1 may also exert hypertensive roles and modulate blood pressure through directly acting on peripheral arterial resistance. Nucleobindin-2 is therefore reported to reduce food intake after administration, mostly refering to the cleaved peptide nesfatin-1. Excess nucleobindin-2/nesfatin-1 in the brain leads to a loss of appetite, lack of the protein in the brain leads to an increase of appetite.