The TSC1–TSC2 complex is a critical negative regulator of mTORC1, which controls cell growth by promoting anabolic processes. This complex, composed of TSC1 (hamartin) and TSC2 (tuberin), functions as a sensor and integrator of growth signals, modulating mTORC1 activity through phosphorylation events. The TSC1–TSC2 complex inhibits mTORC1 by activating the GTPase-activating protein (GAP) activity of TSC2 towards Rheb, a small G-protein. This interaction is essential for controlling cell growth and preventing tumorigenesis. The TSC1–TSC2 complex is also involved in various signaling pathways, including those mediated by Akt, ERK, and IKKβ, which regulate mTORC1 activity. Dysregulation of the TSC1–TSC2 complex leads to aberrant mTORC1 signaling, contributing to tumorigenesis. In TSC, mutations in TSC1 and TSC2 lead to the development of benign tumors, but the complex's role in inhibiting mTORC1 and Akt signaling helps prevent malignant transformation. The TSC1–TSC2 complex also interacts with mTORC2, which phosphorylates Akt, further regulating mTORC1 activity. The complex's regulation by various kinases, including Akt, ERK, and AMPK, highlights its central role in integrating growth signals and maintaining cellular homeostasis. Understanding the molecular mechanisms of TSC1–TSC2 complex regulation is crucial for developing therapeutic strategies targeting mTORC1 in diseases such as TSC and LAM.The TSC1–TSC2 complex is a critical negative regulator of mTORC1, which controls cell growth by promoting anabolic processes. This complex, composed of TSC1 (hamartin) and TSC2 (tuberin), functions as a sensor and integrator of growth signals, modulating mTORC1 activity through phosphorylation events. The TSC1–TSC2 complex inhibits mTORC1 by activating the GTPase-activating protein (GAP) activity of TSC2 towards Rheb, a small G-protein. This interaction is essential for controlling cell growth and preventing tumorigenesis. The TSC1–TSC2 complex is also involved in various signaling pathways, including those mediated by Akt, ERK, and IKKβ, which regulate mTORC1 activity. Dysregulation of the TSC1–TSC2 complex leads to aberrant mTORC1 signaling, contributing to tumorigenesis. In TSC, mutations in TSC1 and TSC2 lead to the development of benign tumors, but the complex's role in inhibiting mTORC1 and Akt signaling helps prevent malignant transformation. The TSC1–TSC2 complex also interacts with mTORC2, which phosphorylates Akt, further regulating mTORC1 activity. The complex's regulation by various kinases, including Akt, ERK, and AMPK, highlights its central role in integrating growth signals and maintaining cellular homeostasis. Understanding the molecular mechanisms of TSC1–TSC2 complex regulation is crucial for developing therapeutic strategies targeting mTORC1 in diseases such as TSC and LAM.