Gout and pseudogout are inflammatory diseases caused by the deposition of monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals in joints. These crystals activate the NALP3 inflammasome, leading to the production of active interleukin (IL)-1β and IL-18. This activation is dependent on caspase-1, ASC, and NALP3. Inflammasome-deficient mice show impaired crystal-induced IL-1β activation and reduced neutrophil influx, indicating the inflammasome's role in inflammation. The NALP3 inflammasome is crucial for processing pro-IL-1β and is involved in several auto-inflammatory diseases. MSU and CPPD crystals activate the NALP3 inflammasome through their surface properties, and this activation is independent of TLR signaling. Colchicine, used to treat auto-inflammatory diseases, blocks IL-1β maturation by inhibiting microtubule assembly, suggesting it acts upstream of inflammasome activation. The findings highlight the inflammasome's role in crystal-induced inflammation and support its importance in auto-inflammatory diseases. The study also shows that the NALP3 inflammasome is involved in other auto-inflammatory conditions, such as familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Inflammasome activation by MSU and CPPD is distinct from that by microbial components, and the inflammasome may recognize danger signals like uric acid. The study provides insights into the molecular mechanisms underlying gout and pseudogout and supports the use of IL-1β inhibitors in their treatment.Gout and pseudogout are inflammatory diseases caused by the deposition of monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals in joints. These crystals activate the NALP3 inflammasome, leading to the production of active interleukin (IL)-1β and IL-18. This activation is dependent on caspase-1, ASC, and NALP3. Inflammasome-deficient mice show impaired crystal-induced IL-1β activation and reduced neutrophil influx, indicating the inflammasome's role in inflammation. The NALP3 inflammasome is crucial for processing pro-IL-1β and is involved in several auto-inflammatory diseases. MSU and CPPD crystals activate the NALP3 inflammasome through their surface properties, and this activation is independent of TLR signaling. Colchicine, used to treat auto-inflammatory diseases, blocks IL-1β maturation by inhibiting microtubule assembly, suggesting it acts upstream of inflammasome activation. The findings highlight the inflammasome's role in crystal-induced inflammation and support its importance in auto-inflammatory diseases. The study also shows that the NALP3 inflammasome is involved in other auto-inflammatory conditions, such as familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Inflammasome activation by MSU and CPPD is distinct from that by microbial components, and the inflammasome may recognize danger signals like uric acid. The study provides insights into the molecular mechanisms underlying gout and pseudogout and supports the use of IL-1β inhibitors in their treatment.