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

The NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammasome complex is a cytosolic multiprotein platform that plays a pivotal role in innate immunity and the maintenance of tissue homeostasis, particularly in the gastrointestinal tract [1, 6]. It is composed of the sensor protein NLRP6, the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD), and the effector protease Caspase-1 or Caspase-11 [1, 13]. Upon activation by microbial components such as lipoteichoic acid (LTA) or viral double-stranded RNA (dsRNA), the complex assembles to facilitate the maturation and secretion of pro-inflammatory cytokines IL-1β and IL-18, as well as the induction of pyroptosis via gasdermin D cleavage [3, 7]. Beyond its inflammatory functions, the NLRP6 inflammasome is essential for regulating goblet cell mucus secretion and shaping the composition of the gut microbiota, thereby protecting against enteric pathogens and colitis [1, 8]. Dysregulation of this complex is associated with a variety of conditions, including inflammatory bowel disease (IBD), colorectal cancer, metabolic syndrome, and sepsis [5, 15]. While no specific NLRP6-targeted drugs are currently approved, the complex is an emerging therapeutic target; research is exploring small-molecule inhibitors, ASC-disrupting agents like IC 100, and the modulation of natural metabolites such as taurine and spermine to treat chronic inflammatory and metabolic diseases [14, 16].

Other names

NALP6PAN3PYPAF5PYRIN-containing APAF1-like protein 5NLRP6 complexNOD-like receptor family pyrin domain containing 6

Inhibition of inflammasome assembly, disruption of ASC speck formation, and modulation of caspase-1/11 activation to prevent the release of pro-inflammatory cytokines IL-1β and IL-18 [1, 16].