While TRPV1 and CSF1R have been demonstrated to activate the NLRP3 inflammasome in astrocytes and microglia cells, it has also been demonstrated that various types of crystals—cholesterol crystals but also calcium phosphate crystals such as hydroxyapatite, which is the relevant crystal type in PXE—can activate inflammasomes through lysosomal rupture and subsequent cathepsin B release (Usui et al., 2012; Yang et al., 2019; Hagan et al., 2020). This evidence concerns the gene CTSB and pseudoxanthoma elasticum (inherited or acquired).