The inflammasome is a key component of innate immunity, mediating the activation of caspase-1 and the processing of pro-IL-1β and pro-IL-18. NLRs, a family of proteins with a nucleotide-binding domain and leucine-rich repeats, are critical mediators of the inflammasome. Studies in gene-deficient mice and cells have shown that NLR inflammasomes are involved in responses to various pathogens, inflammatory diseases, cancer, and metabolic and autoimmune disorders. The activation of the inflammasome in these diseases remains a challenge. This review summarizes recent progress in the field. NLRs are composed of three domains: an N-terminal domain, a central NBD, and a C-terminal LRR. These domains are involved in protein-protein interactions and networks. Several NLRs are associated with large macromolecular complexes. The NLRP3 inflammasome is activated by a diverse series of endogenous and exogenous agonists, but there is no evidence of direct ligand binding. This has led to the hypothesis that NLRP3 senses changes in the cellular environment. Self-activators of the inflammasome include ATP, monosodium urate, calcium pyrophosphate dihydrate, cholesterol crystals, amyloid β, hyaluron, and possibly glucose. Foreign activators include crystalline or particulate structures from exogenous sources, such as asbestos or silica. The NLRP3 inflammasome is also activated by pathogens, including bacteria, viruses, and fungi. For example, NLRP3 can sense bacterial, viral, and fungal pathogens that enter the cytosol. The NLRP3 inflammasome is involved in the pathogenesis of diseases such as gout, Alzheimer's disease, and atherosclerosis. The NLRC4 inflammasome is activated by intracellular flagellin and is involved in the pathogenesis of infections caused by Salmonella, Shigella, Pseudomonas, and Legionella. The AIM2 inflammasome is activated by DNA binding and is involved in the pathogenesis of infections caused by Francisella and DNA viruses. The inflammasome is also involved in the regulation of inflammation and immune responses. Host and microbial inhibitors of the inflammasome have been identified, including pyrin, ASC, and various bacterial and viral proteins. The inflammasome plays a crucial role in innate immunity, and its dysregulation is associated with various diseases, including metabolic disorders and cancer. The NLRP3 inflammasome is particularly involved in metabolic disorders such as obesity, type 2 diabetes, and atherosclerosis. The activation of the inflammasome in these diseases is a complex process involving multiple pathways and factors. The role of the inflammasome in cancer is also being investigated, with evidence suggesting that it may contribute to tumorThe inflammasome is a key component of innate immunity, mediating the activation of caspase-1 and the processing of pro-IL-1β and pro-IL-18. NLRs, a family of proteins with a nucleotide-binding domain and leucine-rich repeats, are critical mediators of the inflammasome. Studies in gene-deficient mice and cells have shown that NLR inflammasomes are involved in responses to various pathogens, inflammatory diseases, cancer, and metabolic and autoimmune disorders. The activation of the inflammasome in these diseases remains a challenge. This review summarizes recent progress in the field. NLRs are composed of three domains: an N-terminal domain, a central NBD, and a C-terminal LRR. These domains are involved in protein-protein interactions and networks. Several NLRs are associated with large macromolecular complexes. The NLRP3 inflammasome is activated by a diverse series of endogenous and exogenous agonists, but there is no evidence of direct ligand binding. This has led to the hypothesis that NLRP3 senses changes in the cellular environment. Self-activators of the inflammasome include ATP, monosodium urate, calcium pyrophosphate dihydrate, cholesterol crystals, amyloid β, hyaluron, and possibly glucose. Foreign activators include crystalline or particulate structures from exogenous sources, such as asbestos or silica. The NLRP3 inflammasome is also activated by pathogens, including bacteria, viruses, and fungi. For example, NLRP3 can sense bacterial, viral, and fungal pathogens that enter the cytosol. The NLRP3 inflammasome is involved in the pathogenesis of diseases such as gout, Alzheimer's disease, and atherosclerosis. The NLRC4 inflammasome is activated by intracellular flagellin and is involved in the pathogenesis of infections caused by Salmonella, Shigella, Pseudomonas, and Legionella. The AIM2 inflammasome is activated by DNA binding and is involved in the pathogenesis of infections caused by Francisella and DNA viruses. The inflammasome is also involved in the regulation of inflammation and immune responses. Host and microbial inhibitors of the inflammasome have been identified, including pyrin, ASC, and various bacterial and viral proteins. The inflammasome plays a crucial role in innate immunity, and its dysregulation is associated with various diseases, including metabolic disorders and cancer. The NLRP3 inflammasome is particularly involved in metabolic disorders such as obesity, type 2 diabetes, and atherosclerosis. The activation of the inflammasome in these diseases is a complex process involving multiple pathways and factors. The role of the inflammasome in cancer is also being investigated, with evidence suggesting that it may contribute to tumor