Slc39a14, also known as ZIP14, is a metal transporter belonging to the SLC39A family. It is involved in transporting metals such as zinc, non-transferrin-bound iron (NTBI), and manganese [5]. Its function is crucial in maintaining metal homeostasis, and it is associated with pathways related to inflammation, metabolism, and iron-related cell death like ferroptosis [1,5]. Genetic models, especially knockout (KO) mouse models, have been instrumental in studying its function.

In KO mouse models, deletion of Slc39a14/Zip14 causes spontaneous intestinal permeability, low-grade chronic inflammation, mild hyperinsulinemia, and insulin resistance in adipose, suggesting its role in modulating the gut microbiome-host metabolism regulation [2]. In pancreatic β-cells, absence of Slc39a14 leads to greater glucose-stimulated insulin secretion, indicating its role in intracellular zinc trafficking and metabolic responses [3]. In vascular smooth muscle cells, inhibition of Slc39a14 alleviates iron overload-induced ferroptosis and vascular calcification [1]. In zebrafish, loss of slc39a14 causes simultaneous manganese hypersensitivity and deficiency, with associated changes in Ca2+ homeostasis and neuronal activity [4].

In conclusion, Slc39a14 is essential for metal homeostasis, influencing multiple biological processes such as metabolism, insulin secretion, and cell death. Studies using KO models have revealed its significance in diseases like vascular calcification, metabolic disorders, and manganese-related neurological conditions, providing valuable insights into potential therapeutic targets for these diseases.