Slc39a10, also known as ZIP10, is a zinc transporter belonging to the SLC39A subfamily. It plays a crucial role in various biological processes by regulating zinc homeostasis. Zinc is essential for many cellular functions, and Slc39a10-mediated zinc transport impacts pathways like MAPK/ERK, PI3K/AKT, and is involved in processes such as hematopoiesis, immune response, and cancer development. Genetic models, especially knockout (KO) and conditional knockout (CKO) mouse models, have been instrumental in understanding its functions [1-5].

In KO/CKO mouse models, hematopoietic Slc39a10-deficient mice display more severe hematopoiesis impairment than those lacking transferrin receptor 1, indicating zinc's significant role in early hematopoietic stem cells (HSCs). Loss of Slc39a10 causes zinc deficiency in fetal HSCs, leading to DNA damage, apoptosis, and G1 cell cycle arrest, which can be restored by zinc supplementation [1]. In T-cell-specific Slc39a10-cKO mice, the loss protects against disease progression in inflammatory bowel disease (IBD) and experimental autoimmune encephalomyelitis (EAE), while inducing massive apoptosis in T cells [5]. Macrophage-specific Slc39a10-knockout mice show lower mortality, reduced liver damage, and decreased circulating inflammatory cytokines upon LPS stimulation due to p53-mediated apoptosis caused by reduced intracellular zinc [4].

In conclusion, Slc39a10 is essential for maintaining zinc homeostasis and is involved in hematopoiesis, immune cell survival, and function. The study of Slc39a10 KO/CKO mouse models has provided valuable insights into its role in diseases such as anemia, autoimmune diseases, and cancer, suggesting it could be a potential therapeutic target for these conditions [1,2,3,5].

References:

1. He, Xuyan, Ge, Chaodong, Xia, Jun, Wang, Fudi, Min, Junxia. 2023. The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2205345. doi:10.1002/advs.202205345. https://pubmed.ncbi.nlm.nih.gov/37068188/

2. Ren, Xiaojuan, Feng, Chao, Wang, Yubo, Ji, Meiju, Hou, Peng. 2023. SLC39A10 promotes malignant phenotypes of gastric cancer cells by activating the CK2-mediated MAPK/ERK and PI3K/AKT pathways. In Experimental & molecular medicine, 55, 1757-1769. doi:10.1038/s12276-023-01062-5. https://pubmed.ncbi.nlm.nih.gov/37524874/

3. Ma, Zuyi, Li, Zhenchong, Wang, Shujie, Huang, Shanzhou, Hou, Baohua. 2021. SLC39A10 Upregulation Predicts Poor Prognosis, Promotes Proliferation and Migration, and Correlates with Immune Infiltration in Hepatocellular Carcinoma. In Journal of hepatocellular carcinoma, 8, 899-912. doi:10.2147/JHC.S320326. https://pubmed.ncbi.nlm.nih.gov/34395329/

4. Gao, Hong, Zhao, Lu, Wang, Hao, Min, Junxia, Wang, Fudi. 2017. Metal transporter Slc39a10 regulates susceptibility to inflammatory stimuli by controlling macrophage survival. In Proceedings of the National Academy of Sciences of the United States of America, 114, 12940-12945. doi:10.1073/pnas.1708018114. https://pubmed.ncbi.nlm.nih.gov/29180421/

5. Shao, Yichang, Mu, Qingdian, Wang, Rong, Min, Junxia, Wang, Fudi. 2025. SLC39A10 is a key zinc transporter in T cells and its loss mitigates autoimmune disease. In Science China. Life sciences, , . doi:10.1007/s11427-024-2817-y. https://pubmed.ncbi.nlm.nih.gov/39862347/