Two disease determining genes, TSCJ and TSC2, have been identified for tuberous sclerosis. Both TSC I and TSC2 have a role as tumor suppressors. Products of these two genes (hamartin and tuberin) fo1·m a complex to function, although its precise physiological activity has not been determined. During the past year, negative regulation of the p70 ribosomal S6 kinase by hamartin and tuberin through the mammalian target of rapamycin (mTOR) has been reported. Including the link between signal transduction associated with S6 kinase activity and tumor development, the molecular mechanism of pathogenesis of tuberous sclerelosis and function of hamartin and tuberin will be elucidated.