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

Solute carrier family 39 member 4 (SLC39A4), also known as ZIP4, is the primary protein responsible for the apical uptake of dietary zinc within the intestinal epithelium (Wang et al., 2002). It belongs to the ZIP family of metal transporters, which are essential for maintaining cellular zinc homeostasis by moving zinc from the extracellular environment or intracellular organelles into the cytosol (UniProt P58143). Mutations in the SLC39A4 gene are the underlying cause of acrodermatitis enteropathica, a severe genetic disorder characterized by impaired zinc absorption, dermatitis, alopecia, and diarrhea (Kury et al., 2002). Beyond its physiological role in nutrition, SLC39A4 is frequently overexpressed in several aggressive malignancies, including pancreatic and liver cancers, where it promotes tumor growth, epithelial-mesenchymal transition, and metastasis (Li et al., 2007; Liu et al., 2011). Consequently, while it is a target for nutritional intervention via zinc supplementation, it is also being investigated as a potential therapeutic target for cancer inhibition. The term Zinc uptake systems in intestinal epithelium is a functional description of the physiological process primarily mediated by this specific molecular transporter.

Other names

ZIP4Zrt- and Irt-like protein 4Acrodermatitis enteropathica zinc transporterZinc transporter ZIP4Zinc uptake systems in intestinal epithelium

SLC39A4 functions as a transmembrane transporter that facilitates the influx of divalent zinc ions (Zn2+) from the intestinal lumen across the apical membrane into the cytoplasm of enterocytes (Geiser et al., 2012). In the context of therapeutic supplementation, high doses of oral zinc salts utilize this and alternative pathways to restore systemic zinc levels in deficiency states (Kury et al., 2002).