The role of NLRP12 in inflammatory diseases

Nucleotide-binding leucine-rich repeat-containing receptor 12 (NLRP12), a highly conserved protein containing an N-terminal pyrin domain (PYD), a nucleotide-binding domain and a C-terminal leucine-rich repeat region, belongs to the nucleotide-binding oligomerization domain-like receptor-containing PYD (NLRP) family and is a cytoplasmic sensor that plays a negative role in inflammation. NLRP12 is involved in multiple disease processes, including formation of inflammasomes and regulation of both canonical and noncanonical inflammatory signaling pathways. NLRP12 and pathogenic infections are closely linked, and alterations in NLRP12 expression and activity are associated with inflammatory diseases. In this review, we begin with a summary of the mechanisms of negative regulation by NLRP12. We then underscore the important roles of NLRP12 in the onset and progression of inflammation, infectious disease, host defense, carcinogenesis and COVID-19. Finally, we highlight factors that influence NLRP12 activity, including synthetic and naturally derived agonists, and are regarded as potential therapeutic agents to overcome inflammatory diseases.