Solute carrier family 39 member 4 (ZIP4) (SLC39A4)

Solute carrier family 39 member 4, commonly known as ZIP4, is a transmembrane protein that serves as the primary gateway for dietary zinc absorption in the small intestine. It functions as a zinc-influx transporter, moving zinc from the intestinal lumen into the cytoplasm of enterocytes to maintain systemic zinc homeostasis. Mutations in the SLC39A4 gene result in acrodermatitis enteropathica, a rare and severe zinc deficiency disorder characterized by dermatitis, alopecia, and diarrhea. Beyond its role in nutrition, ZIP4 is often overexpressed in various malignancies, including pancreatic and hepatocellular carcinomas, where it promotes tumor growth and metastasis by modulating signaling pathways. Consequently, while zinc supplementation is the standard therapy for deficiency caused by ZIP4 malfunction, the protein is also emerging as a potential therapeutic target for cancer inhibition.

Other names

ZIP4Zrt- and Irt-like protein 4Acrodermatitis enteropathica (AE) proteinZinc transporter ZIP4SLC39A4AEZ

ZIP4 facilitates the apical uptake of dietary zinc from the intestinal lumen into enterocytes. Supplements act as substrates that provide high luminal concentrations to overcome transport defects or maintain systemic levels.