Synopsis of major pathways activating mTORC1. mTORC1 is activated by leucine, insulin, IGF-1 and glucose. The activating signals of the growth factors insulin and IGF-1 and the energy source glucose are mediated by attenuating the inhibitory function of TSC2 towards Rheb. The key amino acid leucine activates mTORC1 independent of the TSC2 pathway. Leucine stimulates Rag GTPase-mediated translocation of inactive mTORC1 to endosome/lysosome membranes enriched in activated Rheb. See list of abbreviations.