p62, a protein capable of binding both ubiquitin and autophagy substrates, is well established as a key regulator in cancer and neurodegenerative diseases. Recently, there has been accumulating evidence that p62 is also a pivotal regulator in metabolic diseases, such as obesity, T2DM, NAFLD, metabolic bone disease, gout and thyroid disease. This review summarizes the emerging role of p62 on these diseases by considering its functional domains, phenotypes in genetically modified animals, clinically observed alterations, and its effects on downstream metabolic signaling pathways. At the same time, we highlight the need to explore the roles played by p62 in the gastrointestinal environment and immune system, and the extent to which its elevated expression may confer protection against metabolic disorders.

中文翻译：

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多功能 p62 效应是多种代谢疾病的基础

p62 是一种能够结合泛素和自噬底物的蛋白质，已被公认为癌症和神经退行性疾病的关键调节因子。最近，越来越多的证据表明 p62 也是代谢疾病的关键调节剂，如肥胖、T2DM、NAFLD、代谢性骨病、痛风和甲状腺疾病。本综述通过考虑 p62 的功能域、转基因动物的表型、临床观察到的改变及其对下游代谢信号通路的影响，总结了 p62 在这些疾病中的新作用。同时，我们强调有必要探索 p62 在胃肠道环境和免疫系统中所起的作用，以及它的高表达在多大程度上可以提供针对代谢紊乱的保护。