Zinc transporter ZIP4 (SLC39A4) (ZIP4)

Zinc transporter ZIP4 (SLC39A4) is a vital member of the SLC39A family of zinc transporters, primarily responsible for the uptake of dietary zinc in the small intestine (11.3.3, 11.3.4). It is an eight-transmembrane protein that functions as an H+-powered Zn2+ co-transporter, maintaining cellular and systemic zinc homeostasis (11.2.2, 11.3.5). Mutations in the SLC39A4 gene lead to acrodermatitis enteropathica, a rare and potentially fatal genetic disorder characterized by severe zinc deficiency, which is treated with high-dose oral zinc supplementation (11.2.4, 11.3.4). In oncology, ZIP4 is significantly overexpressed in various malignancies, most notably pancreatic ductal adenocarcinoma and hepatocellular carcinoma (11.1.1, 11.5.2). In these contexts, it acts as an oncogene by increasing intracellular zinc levels, which subsequently activates pro-proliferative and pro-metastatic signaling pathways such as CREB, STAT3, and AKT (11.1.1, 11.2.1). ZIP4 also promotes epithelial-mesenchymal transition (EMT) and contributes to chemotherapy resistance, particularly to gemcitabine (12.1.1, 13.1.2). Due to its high expression on the cell surface and in exosomes, ZIP4 is being explored as both a diagnostic biomarker and a therapeutic target for targeted drug delivery and inhibitory strategies (11.1.3, 12.2.5).

Other names

SLC39A4Solute carrier family 39 member 4Zrt- and Irt-like protein 4AEZAWMS2

Zinc transport into the cytoplasm; activation of oncogenic signaling pathways including CREB, STAT3, and ZEB1