TSC1 (tuberous sclerosis complex subunit 1) is a non-catalytic component of the TSC-TBC complex that functions as a negative regulator of mTORC1, a central nutrient sensor controlling cellular growth 1. The TSC complex acts as a GTPase-activating protein for RHEB, directly inhibiting mTORC1-mediated phosphorylation of translation regulators RPS6KB1/2 and 4E-BP1 12. Within the complex, TSC1 stabilizes TSC2 and prevents its self-aggregation 1. TSC1 also functions as a co-chaperone for HSP90AA1, modulating HSP90AA1 ATPase activity and competing with activating co-chaperone AHSA1 to regulate chaperoning of client proteins including TSC2 itself 3. As a tumor suppressor, TSC1 mutations cause tuberous sclerosis complex (TSC), an autosomal-dominant disorder characterized by multi-organ hamartomas 2. TSC1 mutations represent approximately 20% of pathogenic variants and are predominantly truncating, suggesting a structural role 4. Notably, TSC1-mutant patients generally exhibit milder disease than TSC2-mutant patients, with lower frequencies of seizures, intellectual disability, and severe renal involvement 5. mTOR inhibitors (rapalogues) represent the primary precision medicine approach for TSC-associated manifestations 6, though neuropsychiatric complications remain therapeutically challenging 2.