Zinc transporter ZIP4 (ZIP4)

Zinc transporter ZIP4 (encoded by the SLC39A4 gene) is a transmembrane protein crucial for the uptake of dietary zinc from the small intestine. It is a member of the ZIP (Zrt- and Irt-like Protein) family within the solute carrier 39 (SLC39) family of transporters. ZIP4 embeds in the plasma membrane with eight transmembrane domains and a large extracellular domain. ZIP4 regulation is highly responsive to dietary zinc: expression and membrane localization are upregulated under zinc deficiency and downregulated when zinc is abundant. Loss-of-function mutations in ZIP4 cause acrodermatitis enteropathica, a rare, recessive human disorder marked by zinc deficiency symptoms due to impaired intestinal absorption[5][7]. Elevated ZIP4 expression is linked to poor prognosis in certain cancers, notably pancreatic cancer, where it may contribute to tumor growth and metastasis by altering zinc-dependent signal transduction[4][6]. There are currently no approved therapeutic drugs targeting ZIP4, but it is an emerging biomarker and potential drug target in oncology. Safety concerns for systemic ZIP4 inhibition concern disrupting systemic zinc homeostasis, emphasizing the need for tissue-selective or context-dependent approaches[4][5][6][7].

Other names

SLC39A4Zrt- and Irt-like protein 4Acrodermatitis enteropathica proteinZIP4 transporter

Facilitates zinc influx across the plasma membrane via a uniporter mechanism\nDrugs (experimental) that could inhibit ZIP4 would block zinc uptake