Target of rapamycin complex subunit LST8

MLST8 (target of rapamycin complex subunit LST8) is a shared subunit of both mTORC1 and mTORC2 complexes that regulates cell growth and survival in response to nutrient and hormonal signals (UniProt: Q9BVC4). As part of mTORC1, it enhances mTOR kinase activity and promotes protein, lipid, and nucleotide synthesis while inhibiting autophagy through phosphorylation of ULK1, ATG13, and TFEB. Within mTORC2, MLST8 acts as a bridge between MAPKAP1/SIN1 and mTOR, facilitating growth factor signaling and AKT activation, which coordinates cytoskeletal organization and proliferation (UniProt: Q9BVC4).

No specific tissue distribution or UniProt-annotated disease associations are documented for this protein. MLST8 is implicated in Alzheimer's disease based on proteomics evidence (Chaparral AD proteomics). In post-mortem AD brain tissue compared to age-matched controls, MLST8 shows consistent downregulation with a mean log2 fold-change of −0.40 across a single subcellular fraction in TMT-labeled proteomics analysis. This reduction may reflect compromised mTOR-mediated anabolic signaling and autophagy regulation in the diseased brain.