Nlrp6, also known as NOD-like receptor family pyrin domain containing 6, is a member of the NLR family. It acts as a cytosolic innate immune sensor, recognizing microbe-associated molecular patterns. Nlrp6 is crucial in regulating inflammation, host defense against microbes, and is involved in pathways such as inflammasome activation, NF-κB and MAPK signaling, antiviral IFN signaling, mucus secretion, and AMP production [1,3,6,7]. Genetic models like KO mouse models are valuable for studying its functions.

Nlrp6-deficient mice show reduced inflammasome activation upon mouse hepatitis virus or rotavirus infection, and in steady state stimulated by intestinal microbiota, indicating NLRP6's role in anti-microbial immunity [2]. Nlrp6-/-mice are less susceptible to Listeria monocytogenes infection, associated with reduced pathogen loads and impaired IL-18 production, revealing its role in Gram-positive pathogen infection [4]. Loss of NLRP6 suppresses cell proliferation, colony formation, cell migration, and tumour growth in glioblastoma cells in vitro and in vivo, suggesting its role in tumorigenesis [5]. Also, Nlrp6 depletion in mice leads to cognitive defects and hippocampal NSPC loss, indicating its role in maintaining mitochondrial homeostasis of hippocampal NSPCs [8].

In conclusion, Nlrp6 is a multifaceted gene with essential functions in anti-microbial immunity, maintaining epithelial integrity, and regulating various biological processes. Model-based research, especially Nlrp6 KO mouse models, has revealed its significance in infectious diseases, cancer, and neurodegenerative diseases, providing insights into potential therapeutic targets for these conditions.