Despite the compelling in vitro data supporting the involvement of NLRP3 in the pathogenesis of prion diseases, a study by Nuvolone and colleagues showed that mice lacking NLRP3 (Nlrp3−/−) or the inflammasome adaptor protein ASC (Pycard−/−) succumbed to prion disease, with attack rates and incubation times similar to wild-type mice following inoculation with prions (strain RML) (Nuvolone et al., 2015). This evidence concerns the gene NLRP3 and prion disease.