Snx8, a member of the sorting nexin protein family, plays crucial roles in endocytosis, endosomal sorting, and innate immune response [2]. It is involved in various pathways such as the RIG-I-like receptor (RLR)-mediated innate immune response, IFNγ-triggered noncanonical signaling pathway, and regulation of lysosome reformation [2,3,1]. These functions are of great biological importance as they are related to host defense against pathogens and cellular homeostasis. Genetic models, especially knockout mouse models, have been instrumental in studying Snx8.

In Snx8-deficient mice, several phenotypes related to diseases were observed. In the context of lysosomal storage disorders (LSDs), loss of Snx8 led to phenotypes characteristic of LSDs in human cells, while AAV-based delivery of Snx8 to the brain rescued LSD phenotypes in mice, indicating Snx8's role in lysosome reformation [1]. In response to RNA virus infections, Snx8 -/- mice had lower serum cytokine levels, higher viral titers, and increased lethality, suggesting Snx8 is a positive regulator in the RNA virus-triggered innate immune response [4]. Similarly, for DNA virus HSV-1 infection, Snx8 -/- mice showed lower serum cytokine levels, higher viral titers in the brain, and higher lethality, highlighting Snx8's importance in the innate immune response to DNA viruses [5]. Against Listeria monocytogenes infection, Snx8 -/- mice had lower serum cytokine levels, higher bacterial loads in the liver and spleen, and higher lethality, demonstrating Snx8's role in the IFNγ-triggered noncanonical signaling pathway for host defense [3].

In conclusion, Snx8 is essential for multiple biological processes including innate immune responses against various pathogens and lysosome reformation. The use of Snx8 knockout mouse models has significantly contributed to understanding its role in disease-related conditions such as LSDs and responses to viral and bacterial infections, providing insights for potential therapeutic strategies.