Zinc Transporter Gene Variants (SLC30A and SLC39A) in Human Disease: From Metal Homeostasis Disruption to Convergent Signaling Pathways.

Zinc, an indispensable trace element, performs critical functions in human physiology. As a versatile cofactor, zinc participates in over 1000 enzymatic reactions and regulates more than 2000 transcription factors, orchestrating diverse cellular signaling pathways. The transmembrane transport of zinc is mediated by specialized transporter proteins, which are categorized into two families: zinc transporters (ZnTs) and Zrt- and Irt-like proteins (ZIPs). These transporters are pivotal for maintaining cellular and systemic zinc homeostasis. Pathogenic variants in ZnT/ZIP genes are associated with a spectrum of severe human diseases. This review systematically examines the pathophysiological connections between ZnT/ZIP gene variants and human diseases, providing a conceptual framework for future mechanistic investigations.