Identifying and exploiting SLC39A14 regulatory mechanisms for the future development of therapeutics

Solute carriers (SLCs) are membrane proteins that mediate the transport of biological and inorganic molecules. SLC39A14 regulates the transport of manganese (Mn) into primarily liver and intestinal cells from the blood. Bi-allelic loss of function (LOF) variants in SLC39A14 lead to an accumulation of blood Mn, which travels to the brain, causes significant deficits in motor function, eventually leads to the patients being non-ambulatory. Accordingly, these patients are diagnosed with Hypermanganesaemia with dystonia 2 (HMNDYT2) and are treated with Mn chelating agents. This treatment removes excess Mn from the blood