In general, more than 30 proteins, including ZnT and ZIP transporters, operate under strict coordinated regulation for the maintenance of systemic and cellular zinc homeostasis in mammals; however, humoral mediators, which indicate the zinc status in a cell or tissue to other organs that import and store zinc, have not been identified in zinc metabolism. This is in contrast to iron metabolism, where a short peptide hormone hepcidin plays a critical role in systemic iron homeostasis (296). The recent finding that a low-molecular-weight (2 kDa) zinc-regulated humoral factor, which is likely induced in zinc deficiency, controls gene expression particularly associated with immune functions and development in smooth muscle cells is interesting (304) and suggests that a short peptide operates as a humoral factor in systemic zinc homeostasis.