TBC1D7 is a non-catalytic component of the TSC-TBC complex that negatively regulates mTORC1, a central nutrient sensor controlling cellular growth 12. The complex functions as a GTPase-activating protein for RHEB, which directly activates mTORC1 kinase activity 12. In nutrient-replete conditions, TBC1D7 becomes phosphorylated by Akt at Ser-124, stabilizing the protein through 14-3-3 binding, which maintains TSC complex-mediated inhibition of mTORC1 and prevents phosphorylation of downstream effectors like RPS6KB1/2 and 4E-BP1 3. However, TBC1D7 also regulates systemic growth independently of TSC through effects on insulin-producing cells, suggesting pleiotropic functions 4. Beyond mTORC1 regulation, TBC1D7 promotes glycolytic metabolism in triple-negative breast cancer cells through TSC-independent mechanisms 5. TSC complex assembly requires HSP90/R2TP chaperone scaffolding, which recruits TBC1D7 to coordinate complex formation 6. Loss-of-function TBC1D7 mutations cause autosomal recessive macrocephaly/megalencephaly syndrome with intellectual disability, celiac disease, and behavioral abnormalities 7, reflecting dysregulated mTORC1 signaling and autophagy impairment 7. Genetic variants affecting TBC1D7 expression modify aspirin's protective effects against colorectal cancer 8.