Recent studies have shown that lysosomal dysfunction and destabilization can lead to inflammasome activation in macrophages in Gaucher disease models.58,59 Furthermore, a compromised lysosomal membrane leads to release of lysosomal cathepsins, which can induce NLRP3 inflammasome activation.48 Here, we demonstrate that prolonged exposure to both rotenone and tebufenpyrad induced lysosomal dysfunction in primed microglial cells, pointing out a probable role for lysosome dysfunction in regulating neuroinflammation. This evidence concerns the gene CTSS and Gaucher disease.