The TMPRSS6 gene encodes a type II transmembrane serine protease known as matriptase-2. This protein is primarily expressed in the liver, and also to a lesser extent in other tissues like the kidney, spleen, and small intestine ^[1]. Its main function is to regulate iron homeostasis by negatively controlling the production of hepcidin, the master iron-regulating hormone ^[2]. Matriptase-2 achieves this by cleaving hemojuvelin, a co-receptor that activates hepcidin production. When this process is impaired, hepcidin levels become inappropriately high, leading to limited iron absorption and release. Mutations in the TMPRSS6 gene are the cause of iron-refractory iron deficiency anemia (IRIDA), a rare disorder characterized by microcytic, hypochromic anemia that responds poorly to oral iron supplements ^[3]. Recent research also suggests associations with other conditions like β-thalassemia and Alzheimer's disease due to its role in iron regulation and its expression in the hippocampus ^[4]. The B6-huTMPRSS6 mouse model was generated by replacing the sequences from upstream of exon 1 to 3’UTR of the mouse Tmprss6 gene with the sequences from upstream of exon 1 to 3’UTR of the human TMPRSS6 gene. This model can be used to study the pathological mechanisms and therapeutic approaches for iron-refractory iron deficiency anemia (IRIDA), as well as for the development of TMPRSS6-targeted drugs.