Zrt- and Irt-like protein 14 (ZIP14) (ZIP14)

Zrt- and Irt-like protein 14 (ZIP14), encoded by the SLC39A14 gene, is a transmembrane protein that functions as a transporter for divalent metal cations, including zinc, iron, and manganese [1, 3]. It is primarily localized to the plasma membrane and is highly expressed in the liver, pancreas, and small intestine, where it facilitates the cellular uptake of these essential metals from the extracellular environment [1, 4]. ZIP14 plays a critical role in systemic manganese homeostasis by mediating the uptake of manganese into hepatocytes for subsequent biliary excretion [2]. Mutations in the SLC39A14 gene lead to hypermanganesemia with dystonia, a severe neurodegenerative disorder characterized by excessive manganese accumulation in the brain [2]. Additionally, ZIP14 is a major pathway for the uptake of non-transferrin-bound iron (NTBI) in the liver, making it a potential therapeutic target for managing iron overload conditions like hemochromatosis [3]. While no specific small-molecule drugs targeting ZIP14 are currently approved, its role in metal-related pathologies and inflammatory responses makes it a subject of intense pharmacological interest [4]. (Sources: [1] UniProt Q15043; [2] Tuschl et al., 2016, Nature Genetics; [3] Jenkitkasemwong et al., 2015, PNAS; [4] Aydemir et al., 2017, JBC).

Other names

Solute carrier family 39 member 14SLC39A14Iron/zinc transporter ZIP14LZT-Hs4LIV-1 subfamily of ZIP transporter 4

Inhibition of divalent metal cation transport across the plasma membrane