Multifunctional p62 Effects Underlie Diverse Metabolic Diseases

Min Long, Xing Li, Li Li, Matthew Dodson, Donna D. Zhang, Hongting Zheng

Research output: Contribution to journalReview articlepeer-review

40 Scopus citations


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. p62, as a ubiquitin binding protein and selective autophagy substrate, is well established as a key regulator in cancer and neurodegenerative diseases, etc. Recent research on p62 has shown that it may also play an important role in metabolic diseases. p62 possesses multiple domains that regulate a range of metabolic processes, including adipogenesis, inflammation, BAT thermogenesis, insulin signaling, oxidative stress and apoptosis, energy, and nutrient balance. p62 may exert these effects in an autophagy-independent or -dependent manner. Altered expression of p62 in patients with metabolic dysfunctions was observed, and this change has been linked with lipid, glucose and bone metabolism changes in genetically modified animals. p62 participates in the regulation of multiple metabolic diseases, including obesity, T2DM, NAFLD, metabolic bone diseases, gout, atherosclerosis, and thyroid diseases, through regulating its downstream metabolic pathways.

Original languageEnglish (US)
Pages (from-to)818-830
Number of pages13
JournalTrends in Endocrinology and Metabolism
Issue number11
StatePublished - Nov 2017


  • autophagy
  • autophagy-independent
  • metabolic diseases
  • p62
  • sequestosome1 (SQSTM1)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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