Slc11a1, also known as Natural resistance associated macrophage protein 1 (NRAMP1), is a phagosomal membrane protein. It encodes a metal ion transporter, regulating macrophage activation and playing a role in innate immunity, autoimmune diseases, and infection [1,2,5,6,7]. It is thought to restrict pathogen growth, for example, by transferring divalent cations across the membrane in monocyte phagolysosomes [7].

In gene-related disease research, Slc11a1 polymorphisms are associated with tuberculosis susceptibility, with certain polymorphisms showing increased odds ratios for tuberculosis [1]. In glioma patients, its expression increases with disease progression, predicting unfavorable prognosis and can stratify patients for different immune activation statuses and treatment responses [3]. In colorectal cancer, it serves as a predictive biomarker for overall survival [4]. In kidney renal clear cell carcinoma (KIRC), SLC11A1 promotes tumor progression by remodeling the tumor microenvironment, and its down-regulation represses cell malignant phenotypes and immune response [5]. Vitamin A deficiency in mice impairs neutrophil-mediated control of Salmonella via reduced Slc11a1 expression, and adoptive transfer of SLC11A1-proficient neutrophils can reduce systemic Salmonella burden [6]. In TB patients, genetic variation and low expression of SLC11A1 may cause immune response impairment [7]. In a murine model of ulcerative colitis, the Slc11a1 gene polymorphism influences dextran sulfate sodium (DSS)-induced colitis [8]. In colorectal cancer, SLC11A1 is associated with tumor microenvironment, poor prognosis, and immunotherapy efficacy [9]. Also, SLC11A1 restricts Salmonella growth through magnesium deprivation in mice [10].

In conclusion, Slc11a1 is crucial for innate immunity and pathogen control, influencing the outcome of various infectious and cancerous diseases. Mouse models, especially those with Slc11a1 gene manipulations, have been instrumental in revealing its role in disease-related biological processes such as pathogen control, tumor progression, and immune response impairment.