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). .