TSC2 (tuberous sclerosis complex subunit 2) is the catalytic component of the TSC-TBC complex, a critical negative regulator of mTORC1 signaling 1. As a GTPase-activating protein (GAP), TSC2 inactivates RHEB, a direct mTORC1 activator, thereby suppressing downstream phosphorylation of translation regulators RPS6KB1/2 and 4E-BP1 12. In nutrient-replete conditions, the TSC complex is inactivated, allowing mTORC1 activation and anabolic processes; conversely, nutrient starvation activates TSC2 to inhibit mTORC1 13. TSC2 is regulated by Akt-dependent phosphorylation, linking growth factor signaling to mTOR control 1. TSC2 mutations cause tuberous sclerosis complex (TSC), an autosomal-dominant disorder characterized by widespread hamartomas 4. TSC2 mutations are more common than TSC1 mutations and are associated with more severe phenotypes, including intellectual disability, autism spectrum disorders, and drug-resistant epilepsy 56. Constitutive mTORC1 activation from TSC2 loss drives pathological cell growth in multiple tissues, including renal neoplasms and pulmonary vascular disease 78. mTOR inhibitors (rapamycin, everolimus) represent precision medicine approaches for TSC management 4.