2.A.5.4.5
Zip14 Zn²⁺/Fe²⁺/Mn²⁺/Cd²⁺ uptake transporter (mobilized to the sinusoidal membrane of the hepatocyte during acute inflammation) (Jenkitkasemwong et al. 2012; Pinilla-Tenas et al., 2011); K_M for Fe²⁺= 0.002 μM.  The prion gene family may have descended from an ancestral LZT gene (Ehsani et al. 2012).  The gene is upregulated by iron loading (Nam et al. 2013). LIV-1 ZIP ectodomain shedding in prion-infected mice resembles the cellular response to transition metal starvation (Ehsani et al. 2012).  Zip14 promotes cellular assimilation of iron from transferrin (Zhao et al. 2010) and also plays a role in maintaining manganese homeostasis (Xin et al. 2017). SLC39A14 is essential for efficient Mn²⁺ uptake by the liver and pancreas, and its deficiency results in impaired Mn²⁺ excretion and accumulation of the metal in other tissues (Jenkitkasemwong et al. 2018). Mutations cause hypermanganesemia associated with infantile onset dystonia (Juneja et al. 2018).  SLC39A14 and SLC30A1 increased cellular sensitivity to cadmium (Ferdigg et al. 2025). .