Research progress on the molecular structure, function, and application in tumor therapy of zinc transporter ZIP4

ZIP4, a pivotal member of the ZIP family, is the causative gene for the hereditary disorder AE (acrodermatitis enteropathica) in humans, and plays an essential role in regulating zinc ion balance within cells. While research on the molecular structure of ZIP4 continues, there remains a lack of full understanding regarding the stereo-structural conformation of ZIP4 molecules. Currently, there are two hypotheses concerning the transport of zinc ions into the cytoplasm by ZIP4, with some contradictions between experimental studies. Recent investigations have revealed that ZIP4 is involved in tumor growth, metastasis, drug tolerance, and various other processes. Most studies suggest that ZIP4 regulates the malignant biological behavior of tumors through zinc ions as a second messenger: however, latest research has identified that ZIP4 itself binds to Ephrin-B1 to regulate tumor metastasis. This review provides a comprehensive summary of the molecular structure of ZIP4 and its mechanism for transporting zinc ions while also exploring mutual regulation between zinc ions and ZIP4. Furthermore, it summarizes recent research progress on the role of ZIP4 in tumors and discusses its potential as a target for anticancer therapy based on an extensive analysis of research findings. These insights can guide future investigations into the role of ZIP4 in tumors.