The study by Martinon et al. investigates the molecular mechanisms underlying the inflammatory responses associated with gout and pseudogout, which are characterized by the deposition of monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals in joints and periarticular tissues. The authors demonstrate that MSU and CPPD crystals activate the NALP3 (cryopyrin) inflammasome, leading to the production of active interleukin (IL)-1β and IL-18. Macrophages from mice deficient in components of the inflammasome, such as caspase-1, ASC, and NALP3, are defective in crystal-induced IL-1β activation. Additionally, an impaired neutrophil influx is observed in an in vivo model of crystal-induced peritonitis in inflammasome-deficient mice or mice lacking the IL-1β receptor (IL-1R). These findings provide insights into the molecular processes underlying gout and pseudogout and highlight the pivotal role of the inflammasome in auto-inflammatory diseases. The study also suggests that colchicine, a drug used to treat these conditions, may act by blocking crystal-induced IL-1β maturation upstream of inflammasome activation.The study by Martinon et al. investigates the molecular mechanisms underlying the inflammatory responses associated with gout and pseudogout, which are characterized by the deposition of monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals in joints and periarticular tissues. The authors demonstrate that MSU and CPPD crystals activate the NALP3 (cryopyrin) inflammasome, leading to the production of active interleukin (IL)-1β and IL-18. Macrophages from mice deficient in components of the inflammasome, such as caspase-1, ASC, and NALP3, are defective in crystal-induced IL-1β activation. Additionally, an impaired neutrophil influx is observed in an in vivo model of crystal-induced peritonitis in inflammasome-deficient mice or mice lacking the IL-1β receptor (IL-1R). These findings provide insights into the molecular processes underlying gout and pseudogout and highlight the pivotal role of the inflammasome in auto-inflammatory diseases. The study also suggests that colchicine, a drug used to treat these conditions, may act by blocking crystal-induced IL-1β maturation upstream of inflammasome activation.