Zinc networks: The cell-specific compartmentalization of zinc for specialized functions

Zinc (Zn²⁺) is the most abundant trace element in cells and is essential for a vast number of catalytic, structural, and regulatory processes. Mounting evidence indicates that like calcium (Ca²⁺), intracellular Zn²⁺ pools are redistributed for specific cellular functions. This occurs through the regulation of 24 Zn²⁺ transporters whose localization and expression is tissue and cell specific. We propose that the complement and regulation of Zn²⁺ transporters expressed within a given cell type reflects the function of the cell itself and comprises a Zn ²⁺ network.' Importantly, increasing information implicates perturbations in the Zn²⁺ network with metabolic consequences and disease. Herein, we discuss our current understanding of Zn²⁺ transporters from the perspective of a Zn²⁺ network in four specific tissues with unique Zn²⁺ requirements (mammary gland, prostate, pancreas, and brain). Delineating the entire Zn²⁺ transporting network within the context of unique cellular Zn²⁺ needs is important in identifying critical gaps in our knowledge and improving our understanding of the consequences of Zn²⁺ dysregulation in human health and disease.