TFEB is a master transcription factor regulating lysosomal biogenesis, autophagy, and cellular metabolism 1. It recognizes E-box and CLEAR-box sequences in target gene promoters, particularly genes encoding lysosomal and autophagy-related proteins 2. TFEB activity is dynamically regulated by nutrient availability through mTOR-dependent phosphorylation: during nutrient sufficiency, mTOR phosphorylates TFEB, retaining it in the cytoplasm and suppressing its transcriptional activity 3. Upon starvation or lysosomal stress, mTOR inhibition allows TFEB dephosphorylation and nuclear translocation, activating target gene expression 1. Beyond canonical autophagy-lysosomal functions, TFEB regulates immune responses—the cGAS-STING pathway activates TFEB to enhance lysosomal biogenesis and pathogen clearance 4, while bacterial infection triggers itaconate-mediated TFEB activation for antibacterial immunity. Post-translational modifications like lactylation stabilize TFEB by preventing ubiquitin-mediated degradation, elevating autophagy in cancer cells 5. In placental development, TFEB promotes trophoblast syncytialization independent of its lysosomal regulatory role 6. These mechanisms establish TFEB as a central metabolic and immune sensor, positioning it as a therapeutic target for lysosomal storage disorders and neurodegenerative diseases 7.