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The activity of TFEB depends on its subcellular localisation, turnover, and DNA\u2010binding capacity, all of which are regulated at the post\u2010translational level. Pathological states are characterised by a specific set of stressors, which elicit post\u2010translational modifications that promote gain or loss of TFEB function in the affected tissue. In turn, the resulting increase or decrease in survival of the tissue in which TFEB is more or less active, respectively, may either benefit or harm the organism as a whole. In this way, the post\u2010translational modifications of TFEB account for its otherwise paradoxical protective and deleterious effects on organismal fitness in diseases ranging from neurodegeneration to cancer. In this review, we describe how the intracellular environment characteristic of different diseases alters the post\u2010translational modification profile of TFEB, enabling cellular adaptation to a particular pathological state.<\/jats:p>","DOI":"10.15252\/embr.202357574","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T05:21:00Z","timestamp":1695187260000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["The post\u2010translational regulation of transcription factor EB (TFEB) in health and disease"],"prefix":"10.1038","volume":"24","author":[{"given":"Michael","family":"Takla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3663-3574","authenticated-orcid":false,"given":"Swati","family":"Keshri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5002-5263","authenticated-orcid":false,"given":"David C","family":"Rubinsztein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,20]]},"reference":[{"key":"BFEMBR202357574_CR1","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1126\/science.aan6298","volume":"358","author":"M Abu\u2010Remaileh","year":"2017","unstructured":"Abu\u2010Remaileh M, Wyant GA, Kim C, Laqtom NN, Abbasi M, Chan SH, Freinkman E, Sabatini DM (2017) Lysosomal metabolomics reveals V\u2010ATPase\u2010 and mTOR\u2010dependent regulation of amino acid efflux from lysosomes. 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