The zinc sensing receptor, ZnR/GPR39, in health and disease

Laxmi Sunuwar, David Gilad, Michal Hershfinkel

Research output: Contribution to journalReview articlepeer-review

28 Scopus citations


While zinc has had a well-established structural role for many years, it is only during the last two decades that its role as a signaling molecule has been recognized. Ionic zinc, Zn2+, that is endogenously released during physiological activity acts as a first messenger, triggering the activity of a distinct Zn2+-sensing-receptor, ZnR. The ZnR is a member of the Gq-coupled receptor family, and the molecular moiety mediating its activity is GPR39. In this review, we will discuss the role of the ZnR/GPR39 in mediating Zn2+-dependent signaling in epithelial tissues and in neurons, where Zn2+ homeostasis plays physiological as well as pathological roles. Importantly, ZnR/GPR39 activates signaling that regulates a remarkably wide range of cell functions, including proliferation, differentiation and survival, as well as modulation of ion transport, and thereby, regulation of Na+, H+ and Cl- homeostasis. Moreover, signaling activated by ZnR/GPR39 plays a key role in mediating effects of Zn2+ in health and disease. Thus, ZnR/GPR39 provides a unique target for therapeutically modifying the actions of zinc in a specific and selective manner.

Original languageEnglish
Pages (from-to)1469-1492
Number of pages24
JournalFrontiers in Bioscience - Landmark
Issue number9
StatePublished - 1 Mar 2017


  • Colon
  • Epithelium
  • GPR39
  • Intestine
  • Keratinocyte
  • Neuron
  • Review
  • Zinc
  • Zinc signaling

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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