Cellular response to nutrient status An intricate regulatory mechanism is taking shape around control of the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase complex. Physiological responses of cells to nutrient abundance is regulated by signaling through mTORC1, which interacts with a complex of other proteins at the lysosome that includes small guanosine triphosphatases (GTPases), GTPase-activating proteins, and others. Lawrence et al. present a cryo–electron microscopy structure and biochemical experiments that reveal that the small GTPases act in unanticipated ways in the complex. The tumor suppressor folliculin (FLCN), along with FLCN-interacting protein 2, interacts with its partner GTPase RagC in both active and inactive states, suggesting that a particularly elaborate and stringent regulatory mechanism is at work. Science , this issue p. 971