TFEB (Transcription factor EB)

TFEB (transcription factor EB) is a basic helix-loop-helix protein. It works as a master switch for autophagy and for building lysosomes (the cell's recycling centers that keep your cells tidy). It binds a shared DNA motif called the CLEAR element (Coordinated Lysosomal Expression and Regulation). Through it, TFEB turns on a coordinated set of genes: lysosomal digestive enzymes, lysosomal membrane proteins, and core autophagy genes like the ATG family. When nutrients are plentiful, mTORC1 (sitting on the lysosome surface) tags TFEB at spots including Ser211. That creates a docking site for a 14-3-3 protein, which holds TFEB out in the cytoplasm. But starvation, lysosomal stress, or drugs that block mTORC1 strip those tags off. TFEB then moves into the nucleus and switches on the CLEAR network. In aging models, sustained TFEB activity clears damaged proteins and organelles better, and it has been linked to improved proteostasis (protein quality control).

Last reviewed: June 22, 2026

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