Slfn2, also known as Schlafen 2, is a cytoplasmic protein involved in multiple biological functions. It plays a crucial role in T cell-mediated immunity by protecting transfer RNAs (tRNAs) from stress-induced cleavage, countering the translation-repression caused by reactive oxygen species (ROS) in activated T cells [1]. It also modulates the NF-κB pathway to regulate type I interferon responses, influencing the transcription of IFN-stimulated genes (ISGs) [2]. Additionally, it is associated with maintaining quiescence in T cells, monocytes, and adult murine hematopoietic stem cells, which is important for the normal function and survival of these cells [3,4,5,6].

In Slfn2 -mutant mouse models such as elektra, several phenotypes have been observed. T cells and monocytes from these mice show loss of quiescence, resulting in elevated de novo sterol synthesis, enhanced susceptibility to infection, and diminished numbers of these cells due to apoptosis [4,5]. In the context of T -cell acute lymphoblastic leukemia (T -ALL), targeting Slfn2 to disrupt T -cell quiescence can prevent the development and progression of the disease, potentially offering a new therapeutic strategy [7]. Moreover, Slfn2 is required for normal osteoclast differentiation, as its loss -of -function in mice leads to an osteopetrotic phenotype [8].

In conclusion, Slfn2 is essential for maintaining immune cell quiescence, regulating interferon responses, and enabling T cell -mediated immunity. The Slfn2 KO/CKO mouse models, like the elektra mouse, have been instrumental in revealing its role in diseases such as immunodeficiency, T -ALL, and osteopetrosis, providing valuable insights into potential therapeutic targets for these conditions.