"Loss of inhibition of mTOR is the basis for tumour formation in tuberous sclerosis. Normally, the hamartin (encoded by the TSC1 gene on chromosome 9q32-34) and tuberin (encoded by the TSC2 gene on chromosome 16p13.3) act as a complex which inactivate the Rheb (Ras homologue enriched in brain) protein. In its active state Rheb stimulates mTORC1. Thus, a mutation in either the TSC1 or TSC2 tumour suppressor genes results in overactivation of the mTOR pathway 1."