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Updated: Mar 7, 2026

Author Spotlight: Exploring Cellular Zinc Regulation Through ZnT1 Functionality
Published on: June 2, 2023
The zinc sensing receptor, ZnR/GPR39, in health and disease
Laxmi Sunuwar1, David Gilad1, Michal Hershfinkel2
1Department of Physiology and Cell Biology and The Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion university of the Negev, Beer Sheva, Israel.
Abstract:
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.
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