Slc39a3, also known as Zip3, is a member of the SLC39 family and functions as a zinc (Zn) transporter. It is involved in maintaining cellular zinc homeostasis, which is crucial for various biological processes [1,3,4].

In lactating mammary gland, Zip3-null mouse models revealed that Zip3 is expressed in secretory mammary cells and localizes to the luminal membrane. It does not play a major role in Zn import from the maternal circulation but is involved in the reuptake and cellular retention of Zn from the previously secreted milk pool, regulating cellular function. Additionally, Zip3-null mice showed altered mammary tissue architecture, increased apoptosis, and reduced gland weight [1].

In the hippocampus, knockout of both Slc39a1 and Slc39a3 in mice slowed passive Zn uptake into CA1 neurons and attenuated kainic acid-induced in vivo CA1 cell damage, suggesting a role in neurodegeneration [2].

Mice lacking Zip3 were viable and fertile under normal conditions, but showed a subtle increase in sensitivity to abnormal embryo morphogenesis and thymic pre-T cell depletion when stressed with a zinc-deficient diet, indicating an ancillary role in zinc homeostasis [3].

In conclusion, Slc39a3 is essential for zinc reuptake in lactating mammary glands and may play a role in neurodegeneration and zinc homeostasis. Gene-knockout mouse models have provided valuable insights into its functions in these biological processes, which could potentially contribute to understanding related diseases such as those associated with abnormal zinc metabolism in the mammary gland and neurodegenerative conditions [1,2,3].