{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTSC1, encoding the hamartin protein, functions primarily as a core component of the TSC1–TSC2 complex that negatively regulates mTOR‐dependent signaling. Through its role in this complex, TSC1 stabilizes tuberin (TSC2) and, in concert, promotes the GTPase‐activating function toward Rheb, thereby inhibiting mTOR complex 1 (mTORC1)–mediated phosphorylation events that control protein synthesis, cell growth, and metabolism. In addition, dynamic post‐translational modifications of TSC1—including phosphorylation during cell cycle progression and interactions with regulatory partners such as Hsp90—contribute to fine‐tuning its activity and modulating cellular stress responses and translational control."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its central role in mTOR regulation, alterations in TSC1 contribute to a spectrum of developmental and clinical phenotypes. In patients and animal models, TSC1 mutations are generally associated with a relatively milder form of tuberous sclerosis compared to TSC2 defects, yet loss of TSC1 function in neural progenitors leads to aberrant neuronal development, including dysregulated axon formation, cortical tuber formation, and epileptogenesis. Mosaic inactivation and a “second‐hit” mechanism have been detailed in studies of brain lesions and other hamartomas, underscoring its importance in proper tissue and organ development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also implicates TSC1 in the regulation of cell size, metabolic homeostasis, and tumorigenesis across various tissues. Alterations in TSC1 expression or function, often targeted by microRNAs, have been linked to oncologic processes in renal, bladder, hepatic, and oral cancers, as well as in neoplasms with eosinophilic features. 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