Tuberous sclerosis 2 protein (TSC2)

Tuberous sclerosis 2 protein (TSC2), commonly known as Tuberin, is a large (~200 kDa) tumor suppressor protein encoded by the *TSC2* gene. TSC2 forms a protein complex with Hamartin (TSC1) and TBC1D7, acting primarily as a GTPase-activating protein (GAP) for the small GTPase Rheb, thereby inhibiting the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. By negatively regulating mTORC1, TSC2 controls cell growth, proliferation, protein synthesis, and autophagy. Inactivating mutations in TSC2 underlie the genetic disorder tuberous sclerosis complex, which is characterized by benign tumors in multiple organs and increased risk for neurological and other systemic manifestations. TSC2 also plays roles in regulating cell cycle progression (notably G2/M transition), cell adhesion, migration, and responses to environmental signals such as nutrients and growth factors. Pharmacological targeting of the mTOR pathway is the principle therapeutic strategy for TSC2-deficient disease states.

Other names

TuberinTSC2TSC4LAMPPP1R160protein phosphatase 1, regulatory subunit 160tuberous sclerosis 2 protein

mTOR inhibition via targeting the mTOR pathway directly with drugs (e.g., sirolimus, everolimus) in patients with TSC2 mutations or mTOR hyperactivity. Potentially indirectly stabilizing/restoring Tuberin function (therapies in development).