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The mechanisms that lead to the generation of gallstones remain unclear. By analysing human biliary sludge (small stones in biliary fluid) and larger gallstones, Munoz et al. identify key signs of the presence of neutrophil extracellular traps (NETs), including deposits of extracellular DNA and robust neutrophil elastase activity (involved in NET formation). A series of studies using human neutrophils and gallstones confirmed a role of NETs in gallstone formation and growth. Genetic and pharmaceutical inhibition of NET formation or neutrophil activity effectively prevented and treated gallstones in mice.