How cellular Zn2+ signaling drives physiological functions
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Updated: Feb 6, 2026

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Published on: March 21, 2025
Noam Levaot1, Michal Hershfinkel1
1Department of Physiology and Cell Biology and The Zlotowski Center for Neuroscience, Faculty of Health Sciences, POB 653, Ben-Gurion Ave., Ben-Gurion University of the Negev, Beer Sheva, 84105, Israel.
Abstract:
Zinc is an essential micronutrient affecting many aspects of human health. Cellular Zn2+ homeostasis is critical for cell function and survival. Zn2+, acting as a first or second messenger, triggers signaling pathways that mediate the physiological roles of Zn2+. Transient changes in Zn2+ concentrations within the cell or in the extracellular region occur following its release from Zn2+ binding metallothioneins, its transport across membranes by the ZnT or ZIP transporters, or release of vesicular Zn2+. These transients activate a distinct Zn2+ sensing receptor, ZnR/GPR39, or modulate numerous proteins and signaling pathways. Importantly, Zn2+ signaling regulates cellular physiological functions such as: proliferation, differentiation, ion transport and secretion. Indeed, novel therapeutic approaches aimed to maintain Zn2+ homeostasis and signaling are evolving. This review focuses on recent findings describing roles of Zn2+ and its transporters in regulating physiological or pathological processes.
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