转录因子EB（TFEB）是一种基本螺旋-环-螺旋亮氨酸拉链转录因子，作为溶酶体生物发生、溶酶体胞吐和巨噬细胞自噬的主要调控因子。TFEB对多种生理功能起到贡献，包括线粒体生物发生以及先天和适应性免疫应答。因此，TFEB是细胞对从营养限制到病原侵袭的压力因子的适应的必要组成部分。TFEB的活性取决于其亚细胞定位、周转率和DNA结合能力，这些都在翻译后的水平上受到调控。病理状态表现为一组特定的压力因子，这些压力因子引发了促进所受组织中TFEB功能增强或减弱的翻译后修饰。反过来，受影响组织中TFEB活跃度的增加或减少对整个生物体可能带来益处或危害。通过这种方式，TFEB的翻译后修饰解释了其在从神经退行性疾病到癌症等疾病中对生物体适应度产生相互矛盾的保护和有害效应的机制。在本综述中，我们描述了不同疾病的细胞内环境如何改变TFEB的翻译后修饰谱，使细胞能够适应特定的病理状态。© 2023 年作者。在CC BY 4.0许可证条款下发表。

Transcription factor EB (TFEB) is a basic helix-loop-helix leucine zipper transcription factor that acts as a master regulator of lysosomal biogenesis, lysosomal exocytosis, and macro-autophagy. TFEB contributes to a wide range of physiological functions, including mitochondrial biogenesis and innate and adaptive immunity. As such, TFEB is an essential component of cellular adaptation to stressors, ranging from nutrient deprivation to pathogenic invasion. The activity of TFEB depends on its subcellular localisation, turnover, and DNA-binding capacity, all of which are regulated at the post-translational level. Pathological states are characterised by a specific set of stressors, which elicit post-translational 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-translational 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-translational modification profile of TFEB, enabling cellular adaptation to a particular pathological state.© 2023 The Authors. Published under the terms of the CC BY 4.0 license.