Slc30a9, also known as ZnT9, is a mitochondria-resident zinc transporter. It plays a crucial role in maintaining mitochondrial zinc homeostasis, which is essential for various biological processes. This function is likely associated with its impact on the activities of respiration complexes, and it may be involved in pathways like Wnt signalling, though evidence on the latter is inconsistent [2,3]. Its normal function is of great biological importance, especially in mammalian early embryonic development [1].

In Drosophila melanogaster, knockdown of ZnT9 (ZnT49B) leads to impaired movement, mitochondrial deformation, and pupal lethality. The defect can be partially rescued by mouse ZnT9 expression or a zinc chelator, indicating zinc dyshomeostasis [1]. In mice, germline loss of Znt9 results in mid-gestational lethality with severe developmental abnormalities. Targeted mutagenesis in the mouse brain causes serious dwarfism, physical incapacitation, and death, along with almost non-existent GH/IGF-1 signals [1]. In humans, mutations in SLC30A9 are linked to a novel cerebro-renal syndrome. Cytosolic Zn2+ measurements in HEK293 cells overexpressing wild-type and mutant SLC30A9 suggest that the mutation affects intracellular zinc homeostasis [2].

In conclusion, Slc30a9 is a key mitochondrial zinc transporter essential for mammalian development. Studies using gene knockout (KO) models in flies and mice, along with human cell-based experiments, have revealed its role in maintaining zinc homeostasis and its significance in preventing diseases like the cerebro-renal syndrome. These models have provided valuable insights into the biological functions of Slc30a9 and its implications in disease conditions.