NOD-like receptor family pyrin domain-containing protein 6 (NLRP6)

NOD-like receptor family pyrin domain-containing protein 6 (NLRP6) is a cytosolic pattern recognition receptor belonging to the nucleotide-binding domain and leucine-rich repeat containing (NLR) family. It acts as an innate immune sensor that recognizes microbe-associated molecular patterns. Upon activation, NLRP6 recruits the adaptor ASC and inflammatory caspases such as caspase‑1 or caspase‑11 to form the NLRP6 inflammasome, which mediates maturation and secretion of pro-inflammatory cytokines IL‑18 and IL‑1β, leading to pyroptotic cell death. NLRP6 is highly expressed in intestinal epithelial cells where it regulates gut microbiota composition, goblet cell mucus secretion, tissue homeostasis, and susceptibility to gastrointestinal inflammatory diseases. It also has roles in extra-intestinal tissues such as the liver. Tight regulation of its activity is critical; dysregulation can contribute to colitis, infection susceptibility, or cancer development. Structurally, NLRP6 contains a pyrin domain that self-associates into filaments for inflammasome assembly via PYD–PYD interactions with ASC. Its activation can be modulated by microbial metabolites. Currently there are no known drugs directly targeting NLRP6 nor established clinical biomarkers or safety concerns specific for this target reported in available literature. References supporting these statements include peer-reviewed reviews on its structure-function relationships, disease associations, mechanistic studies, expression patterns, and structural biology data.

Other names

NLRP6 inflammasomeNod-like receptor family pyrin domain containing 6NALP6