Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder that is caused by mutation in either the TSC1 (hamartin) or TSC2 (tuberin) gene. TSC1 and TSC2 proteins form a physical and functional heterodimer in vivo that inhibits ribosomal protein S6 kinase 1 (S6K1) and activates eukaryotic initiation factor 4E-bindingprotein 1 (4E-BP1) by inhibition of the mammalian target of rapamycin (mTOR). TSC2 belongs to small GTPase protein of the Ras superfamily, contain a Rap-GAP domain. Predicted molecular weight 201 kD. Ser664 TSC2 phosphorylation leads to TSC1-TSC2 dissociation and markedly impairs TSC2 ability to inhibit mTOR signaling, cell proliferation, and oncogenic transformation. Erk (extracellular signal-regulated kinase) may contribute to tumorigenesis by phosphorylating TSC2 at specific residues, particularly S664.