The invention relates to the identification of isovaleric acid as a natural ligand of the RCC356 G-protein coupled receptor (GPCR). The invention encompasses the use of the interaction of RCC356 polypeptides and isovaleric acid as the basis of screening assays for agents that modulate the activity of the RCC356 receptor. The invention also encompasses diagnostic and other assays performed based upon the RCC356/isovaleric acid interaction, as well as kits for performing diagnostic and screening assays.