The pyrin inflammasome is a key player in pediatric autoinflammatory diseases (AIDs), playing a central role in several monogenic AIDs, including familial Mediterranean fever (FMF) and mevalonate kinase deficiency (MKD). The pyrin inflammasome is activated through various molecular pathways, including the disruption of RhoA GTPases by pathogen toxins, phosphorylation of pyrin residues by kinases PKN1/2, and the binding of the chaperone 14-3-3. The activation of the pyrin inflammasome leads to the cleavage and activation of pro-caspase-1, resulting in the production of pro-inflammatory cytokines such as IL-1β and IL-18. Gasdermin D (GSDMD) is also involved in pyroptosis, a form of programmed cell death that helps eliminate intracellular pathogens and recruit immune cells to the site of damage. Recent studies have highlighted the role of steroid hormone catabolites and alarmins S100A8/A9 and S100A12 in pyrin-dependent inflammation. The pyrin inflammasome is regulated by various molecular mechanisms, including the interaction with the cytoskeleton and the B30.2/SPRY domain. The MEFV gene, located on chromosome 16p13.3, encodes the pyrin protein, and mutations in this gene are associated with various AIDs. The pyrin inflammasome is involved in the pathogenesis of several AIDs, including FMF, PAAND, and MKD. The treatment of these diseases often involves the use of IL-1 inhibitors, such as anakinra and canakinumab, as well as colchicine for FMF. The management of these diseases requires a comprehensive understanding of the molecular pathways involved and the genetic factors that contribute to their development.The pyrin inflammasome is a key player in pediatric autoinflammatory diseases (AIDs), playing a central role in several monogenic AIDs, including familial Mediterranean fever (FMF) and mevalonate kinase deficiency (MKD). The pyrin inflammasome is activated through various molecular pathways, including the disruption of RhoA GTPases by pathogen toxins, phosphorylation of pyrin residues by kinases PKN1/2, and the binding of the chaperone 14-3-3. The activation of the pyrin inflammasome leads to the cleavage and activation of pro-caspase-1, resulting in the production of pro-inflammatory cytokines such as IL-1β and IL-18. Gasdermin D (GSDMD) is also involved in pyroptosis, a form of programmed cell death that helps eliminate intracellular pathogens and recruit immune cells to the site of damage. Recent studies have highlighted the role of steroid hormone catabolites and alarmins S100A8/A9 and S100A12 in pyrin-dependent inflammation. The pyrin inflammasome is regulated by various molecular mechanisms, including the interaction with the cytoskeleton and the B30.2/SPRY domain. The MEFV gene, located on chromosome 16p13.3, encodes the pyrin protein, and mutations in this gene are associated with various AIDs. The pyrin inflammasome is involved in the pathogenesis of several AIDs, including FMF, PAAND, and MKD. The treatment of these diseases often involves the use of IL-1 inhibitors, such as anakinra and canakinumab, as well as colchicine for FMF. The management of these diseases requires a comprehensive understanding of the molecular pathways involved and the genetic factors that contribute to their development.