| Summary: | Zinc (Zn<sup>2+</sup>) plays an essential role in epithelial physiology. Among its many effects, most prominent is its action to accelerate cell proliferation, thereby modulating wound healing. It also mediates affects in the gastrointestinal system, in the testes, and in secretory organs, including the pancreas, salivary, and prostate glands. On the cellular level, Zn<sup>2+</sup> is involved in protein folding, DNA, and RNA synthesis, and in the function of numerous enzymes. In the mammary gland, Zn<sup>2+</sup> accumulation in maternal milk is essential for supporting infant growth during the neonatal period. Importantly, Zn<sup>2+</sup> signaling also has direct roles in controlling mammary gland development or, alternatively, involution. During breast cancer progression, accumulation or redistribution of Zn<sup>2+</sup> occurs in the mammary gland, with aberrant Zn<sup>2+</sup> signaling observed in the malignant cells. Here, we review the current understanding of the role of in Zn<sup>2+</sup> the mammary gland, and the proteins controlling cellular Zn<sup>2+</sup> homeostasis and signaling, including Zn<sup>2+</sup> transporters and the Gq-coupled Zn<sup>2+</sup> sensing receptor, ZnR/GPR39. Significant advances in our understanding of Zn<sup>2+</sup> signaling in the normal mammary gland as well as in the context of breast cancer provides new avenues for identification of specific targets for breast cancer therapy.
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