The article reviews the role of NLR (nucleotide-binding domain, leucine-rich repeat containing) proteins in the activation of inflammasomes, which are crucial for the maturation and secretion of pro-inflammatory cytokines IL-1β and IL-18. NLRs are key mediators of innate immunity, responding to a wide range of microbial pathogens, inflammatory diseases, cancer, and metabolic and autoimmune disorders. The review highlights the recent progress in understanding how inflammasomes are activated in these diseases and disease models, emphasizing the complex interplay between host recognition, signal initiation, and resolution. It also discusses the specific functions of NLRs such as NLRP3, NLRC4, and NLRP1, and their roles in various inflammatory conditions, including metabolic disorders and cancer. The article concludes by exploring the potential therapeutic targets for treating metabolic diseases and cancer by inhibiting the inflammasome pathway.The article reviews the role of NLR (nucleotide-binding domain, leucine-rich repeat containing) proteins in the activation of inflammasomes, which are crucial for the maturation and secretion of pro-inflammatory cytokines IL-1β and IL-18. NLRs are key mediators of innate immunity, responding to a wide range of microbial pathogens, inflammatory diseases, cancer, and metabolic and autoimmune disorders. The review highlights the recent progress in understanding how inflammasomes are activated in these diseases and disease models, emphasizing the complex interplay between host recognition, signal initiation, and resolution. It also discusses the specific functions of NLRs such as NLRP3, NLRC4, and NLRP1, and their roles in various inflammatory conditions, including metabolic disorders and cancer. The article concludes by exploring the potential therapeutic targets for treating metabolic diseases and cancer by inhibiting the inflammasome pathway.