A novel receptor for GDF15 was identified (GFRAL), as well as the use of this receptor in the identification or screening of GDF15 agonists or antagonists. These agonist or antagonist compounds may be used to either potentiate or suppress GDF15-like effects, respectively, at the cellular and organism levels, and may be used in treatment of metabolic diseases, including obesity, type 2 diabetes, hyperglycemia, hyperinsulinemia, dyslipidemia, diabetic nephropathy, or anorexia.