Leucine is an essential amino acid that plays an important role in a variety of metabolic processes, including both physiological ones such as insulin secretion and pathological ones involved in the metabolic syndrome. mTORC1 is a key protein that is also involved in many aspects of metabolism and senses leucine through proteins called sestrins. Some aspects of this signaling pathway were previously observed in cultured cells, but now Cangelosi et al. have identified what happens in vivo in a mammal. The authors clarified the signaling steps involved in mTORC1 sensing of leucine through sestrins in mice and determined that the regulation of this pathway varies between different zones within the liver based on proximity to blood vessels. —YN