The functions of ZIP8, ZIP14, and ZnT10 in the regulation of systemic manganese homeostasis

James W.W. Winslow, Kirsten H. Limesand, Ningning Zhao

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations


As an essential nutrient, manganese is required for the regulation of numerous cellular processes, including cell growth, neuronal health, immune cell function, and antioxidant defense. However, excess manganese in the body is toxic and produces symptoms of neurological and behavioral defects, clinically known as manganism. Therefore, manganese balance needs to be tightly controlled. In the past eight years, mutations of genes encoding metal transporters ZIP8 (SLC39A8), ZIP14 (SLC39A14), and ZnT10 (SLC30A10) have been identified to cause dysregulated manganese homeostasis in humans, highlighting the critical roles of these genes in manganese metabolism. This review focuses on the most recent advances in the understanding of physiological functions of these three identified manganese transporters and summarizes the molecular mechanisms underlying how the loss of functions in these genes leads to impaired manganese homeostasis and human diseases.

Original languageEnglish (US)
Article number3304
JournalInternational journal of molecular sciences
Issue number9
StatePublished - May 1 2020


  • Manganese
  • Metabolism
  • Metal transporters
  • ZIP14
  • ZIP8
  • ZnT10

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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