Both diseases are caused by mutations of TSC1 or TSC2 (TSC is tuberous sclerosis complex) that impair GAP (GTPase-activating protein) activity of the TSC1-TSC2 complex for Rheb, leading to inappropriate activity of signalling downstream of mTORC1 (mTOR complex 1). mTOR inhibitors are already used in a variety of clinical settings including as immunosuppressants, anticancer agents and antiproliferative agents in drug-eluting coronary artery stents.
Individuals with tuberous sclerosis complex (TSC) develop astrocytoma-like tumors resulting from mutations in the TSC2 protein, tuberin, which is hypothesized to function as a Rap1 GTPase activating protein (GAP).