Toward unzipping the ZIP metal transporters: structure, evolution, and implications on drug discovery against cancer

The Zrt-/Irt-like protein (ZIP) family consists of divalent metal transporters, ubiquitous in all kingdoms of life. Since the discovery of the first ZIPs in the 1990s, the ZIP family has been expanding to contain tens of thousands of members playing key roles in uptake and homeostasis of life-essential trace elements, primarily zinc, iron and manganese. Some family members are also responsible for toxic metal (particularly cadmium) absorption and distribution. Their central roles in trace element biology, and implications in many human diseases, including cancers, have elicited interest across multiple disciplines for potential applications in biomedicine, agriculture and environmental protection. In this review and perspective, selected areas under rapid progress in the last several years, including structural biology, evolution, and drug discovery against cancers, are summarised and commented. Future research to address the most prominent issues associated with transport and regulation mechanisms are also discussed.

Automated summary

The ZIP protein family plays a crucial role in the uptake and homeostasis of essential trace elements, with some members also responsible for toxic metal absorption. Research has made rapid progress in areas such as structural biology, evolution, and drug discovery related to this family. Future studies aim to address prominent issues associated with transport and regulation mechanisms.