AKT1S1 (PRAS40, proline-rich Akt/PKB substrate 40 kDa) is an mTORC1 accessory protein that binds the mTOR kinase domain. The interaction with mTOR is induced under conditions that inhibit mTOR signalling, such as nutrient or serum deprivation or mitochondrial metabolic inhibition. AKT1S1 binding suppresses mTORC1 phosphorylation of S6K1 and 4E-BP1 (Sancak et al. 2007, Vander Haar et al. 2008, Oshiro et al. 2007) and suppresses constitutive activation of mTOR in cells lacking TSC2. AKT1S1 silencing inactivates insulin-receptor substrate-1 (IRS-1) and Akt, and uncouples the response of mTOR to Akt signals. Furthermore, AKT1S1 phosphorylation by Akt and association with 14-3-3, a cytosolic anchor protein, are crucial for insulin to stimulate mTOR (Sancak et al. 2007, Vander Haar et al. 2008). PRAS40 is also a substrate of the mTOR complex (Kovacina et al. 2003, Oshiro et al. 2007).