Zrt- and Irt-like protein family (ZIP) (ZIP)

The Zrt- and Irt-like protein (ZIP) family, also known as the Solute Carrier Family 39 (SLC39), consists of 14 members in humans that are essential for maintaining cellular zinc homeostasis (Kambe et al., 2015, Physiological Reviews). These transporters primarily function by moving zinc and other divalent metal ions, such as iron and manganese, from the extracellular space or intracellular organelles into the cytoplasm (Jeong and Eide, 2013, Molecular Aspects of Medicine). ZIP proteins play critical roles in various biological processes, including cell signaling, proliferation, and immune function, by regulating the availability of zinc as a structural or catalytic cofactor for thousands of proteins (Hogstrand, 2012, Encyclopedia of Metalloproteins). Dysregulation of ZIP transporters is linked to numerous pathologies, including Acrodermatitis enteropathica (ZIP4 mutations), Ehlers-Danlos syndrome (ZIP13 mutations), and various cancers where specific ZIP members are overexpressed to support rapid cell growth (UniProt Consortium, 2024). Consequently, the ZIP family is an emerging therapeutic target, with research focusing on small molecule inhibitors and antibodies to modulate zinc levels in disease states (Kambe et al., 2015, Physiological Reviews). While direct pharmacological targeting is still largely in the experimental stage, understanding their role in metal transport is vital for developing treatments for metabolic and oncological disorders (Jeong and Eide, 2013, Molecular Aspects of Medicine).

Other names

Solute carrier family 39SLC39 familyZrt- and Irt-like proteinsZIP familyZinc transporter family

ZIP transporters facilitate the influx of zinc and other divalent cations from the extracellular space or intracellular organelles into the cytosol.