mTORC1

Rapamycin complex 1 (mTORC1) is a serine/threonine protein kinase that functions as a central regulator of cell growth, protein synthesis, and metabolism in response to nutrient and growth factor signals^[1][2][3]. Mechanistically, mTORC1 integrates signals from the PI3K/Akt pathway and upstream energy sensors such as AMPK to control ribosomal biogenesis and cap-dependent translation via phosphorylation of S6K and 4E-BP1^[4][5]. Compared with mTORC2, mTORC1 is rapamycin-sensitive and primarily governs anabolic processes, whereas mTORC2 regulates cytoskeletal organization and cell survival^[1][6]. In disease models, dysregulated mTORC1 activity contributes to cancer progression, neurodegeneration, and metabolic disorders, including polycystic kidney disease and excessive alcohol intake^{[7][8][9][10][11]}. Isoform-specific studies reveal that selective inhibition of mTORC1 by rapalogs or ATP-competitive inhibitors allows distinct modulation of downstream pathways without fully affecting mTORC2 functions^[12][1][13]. Agonists or inhibitors targeting mTORC1, such as rapamycin, PP242, and sapanisertib, have demonstrated the ability to reduce pathological growth, restore proteostasis, and regulate cellular energy metabolism, supporting their experimental use in translational research^[1][3][13]. The combination of mTORC1 inhibitors with metabolic regulators or genetic models provides mechanistic insight into mTORC1’s role in cellular homeostasis and offers a framework for developing targeted therapies^[4][13].