MLST8 (MTOR associated protein MLST8) is a critical scaffolding subunit shared by both mTORC1 and mTORC2 complexes, which regulate cell growth and survival in response to nutrient and hormonal signals 1. Within mTORC1, MLST8 interacts directly with MTOR to enhance its kinase activity and stabilize MTOR-RPTOR interactions 2. In response to growth factors or amino acids, mTORC1 is recruited to the lysosome membrane where MLST8 facilitates phosphorylation of substrates including RPS6KB1, RPS6KB2, and EIF4EBP1, promoting protein and lipid synthesis while simultaneously inhibiting catabolic pathways like autophagy by phosphorylating ULK1 and ATG13 3. As a component of mTORC2, MLST8 acts as a bridge between MAPKAP1/SIN1 and MTOR, transducing growth factor signals to regulate proliferation, cytoskeletal organization, and lipogenesis through phosphorylation of AGC kinase family members including AKT and PKC 1. The K63-linked polyubiquitination status of MLST8 (also called GβL) dynamically regulates whether it associates with mTORC1 or mTORC2, with TRAF2-mediated ubiquitination favoring mTORC1 while OTUD7B-mediated deubiquitination promotes mTORC2 assembly 1. MLST8 dysregulation contributes to multiple diseases: elevated MLST8 promotes glioblastoma and renal cell carcinoma progression through enhanced mTOR signaling 4, while MLST8 overexpression in retinal pigment epithelium disrupts autophagy and drives age-related macular degeneration-like pathology 5. Additionally, MLST8 is essential for coronavirus replication through mTORC1-dependent suppression of antiviral autophagy 6.