Online now: Tsang et al. identify the T-type calcium channel Cav3.1 as a neuronal leucine sensor in hypothalamic POMC neurons. Leucine directly binds Cav3.1, lowering its activation threshold. Loss of Cav3.1 in POMC neurons abolishes high-protein diet-induced appetite suppression, while pharmacological activation promotes weight loss and potentiates the effects of anorectic agents.