Neuman, Nicole AHenske, Elizabeth2013-03-292011Neuman, Nicole A, and Elizabeth Petri Henske. 2011. Non-canonical functions of the tuberous sclerosis complex-Rheb signalling axis. EMBO Molecular Medicine 3(4): 189-200.1757-4676http://nrs.harvard.edu/urn-3:HUL.InstRepos:10482557The protein products of the tuberous sclerosis complex (TSC) genes, TSC1 and TSC2, form a complex, which inhibits the small G-protein, Ras homolog enriched in brain (Rheb). The vast majority of research regarding these proteins has focused on mammalian Target of Rapamycin (mTOR), a target of Rheb. Here, we propose that there are clinically relevant functions and targets of TSC1, TSC2 and Rheb, which are independent of mTOR. We present evidence that such non-canonical functions of the TSC-Rheb signalling network exist, propose a standard of evidence for these non-canonical functions, and discuss their potential clinical and therapeutic implications for patients with TSC and lymphangioleiomyomatosis (LAM).en-USJournal Article2013-03-2910.1002/emmm.201100131