Zinc transporter (ZnT/ZIP)

Zinc transporters are a superfamily of membrane proteins that maintain cellular zinc homeostasis by regulating the movement of zinc ions across biological membranes [1, 4]. They are categorized into two primary families: the SLC30 (ZnT) family, which facilitates zinc efflux from the cytoplasm, and the SLC39 (ZIP) family, which promotes zinc influx [4, 15]. These transporters are essential for numerous physiological processes, including protein structure stabilization, enzymatic activity, and cell signaling where zinc acts as a second messenger [1, 23]. Zinc transporter 8 (ZnT8) is particularly notable for its role in insulin maturation and storage in pancreatic beta cells and serves as a major autoantigen in Type 1 Diabetes [3, 20]. Dysregulation of specific zinc transporters is associated with various pathologies, including Type 2 Diabetes, neurodegenerative diseases like Alzheimer's, and several cancers where transporters like ZIP4 and ZIP6 are overexpressed [4, 25, 27]. In oncology, ZIP6 is a target for antibody-drug conjugates like Ladiratuzumab vedotin, which deliver cytotoxic payloads to tumor cells [4, 16]. In immunology, monoclonal antibodies such as mAb43 are being developed to shield ZnT}

Other names

SLC30 familySLC39 familySolute carrier family 30Solute carrier family 39Zrt- and Irt-like proteinZnTZIP

Zinc transporters function by either exporting zinc from the cytoplasm (ZnT family) or importing it into the cytoplasm (ZIP family) to maintain homeostasis [4, 15]. Drugs targeting these transporters act through various mechanisms: monoclonal antibodies like mAb43 bind to extracellular epitopes of ZnT8 to mask them from autoimmune recognition in Type 1 Diabetes [20, 22]; antibody-drug conjugates like Ladiratuzumab vedotin target overexpressed ZIP6 in cancer cells to deliver cytotoxic payloads [4, 16]; and small molecules or supplements modulate transporter activity or expression to correct zinc imbalances in metabolic or genetic disorders [19, 25].