The detailed and differentiated roles of PYY's active species in physiological processes such as insulin secretion, appetite regulation, bone metabolism, and DPP‐4 activity (both natively, and when inhibited pharmacologically), as well as pathophysiological processes such as obesity and intestinal disease can now be investigated with sensitive and specific LC‐MS/MS assays. The gene discussed is PYY; the disease is obesity due to melanocortin 4 receptor deficiency.