Slfn5, also known as Schlafen 5, is a gene with diverse functions. It is involved in multiple biological processes, such as cell-cycle regulation, DNA repair, and immune response. It is associated with pathways like the AKT/GSK-3β/β-catenin, JAK/STAT, and is important for maintaining genomic stability [5,6,7,8]. Genetic models, especially knockout models, are valuable for studying its functions.

In DNA repair, SLFN5 is crucial for 53BP1 topological arrangement at DNA double-strand breaks (DSBs). SLFN5 deficiency disrupts DSB repair topology and impairs non-homologous end joining, telomere fusions, class switch recombination, and sensitivity to poly (ADP-ribose) polymerase inhibitor [1].

In cancer, in ovarian cancer, SLFN5 promotes reversible epithelial and mesenchymal transformation, and its silencing inhibits EMT and invasion of ovarian cancer cells [3]. In breast cancer, SLFN5 can inhibit cell proliferation and colony formation, promote apoptosis by upregulating PTEN transcription via ZEB1, and inhibit the purine metabolic pathway [7]. In triple-negative breast cancer, histone H4K12 lactylation downregulates SLFN5, promoting malignancy [2]. In castration-resistant prostate cancer, SLFN5 regulates LAT1-mediated mTOR activation [4]. In lung cancer, knockdown of Slfn5 alleviates lipopolysaccharide-induced pneumonia by regulating the JAK/STAT pathway [6]. In colorectal adenocarcinoma, SLFN5 is associated with poor survival outcomes and regulates the immune response via the JAK/STAT/IFN-alpha/beta signaling [8].

In summary, Slfn5 plays essential roles in DNA repair, cell-cycle regulation, and cancer-related processes. The use of gene knockout models in mouse studies has significantly contributed to understanding its functions in these specific disease areas, such as various cancers and DNA repair-related disorders [1,2,3,4,6,7,8].