Several exogenous activators of NLRP3, such as asbestos and silica crystals (Dostert et al, 2008; Hornung et al, 2008), and endogenous aggregates, including circulating ASC specks, neuronal amyloid‐β fibrils and multiple myeloma‐associated β2‐microglobulin fibrils (Halle et al, 2008; Franklin et al, 2014; Hofbauer et al, 2021), have been described to undergo a pathway of internalization, endo‐lysosomal trafficking and lysosomal membrane destabilization. This evidence concerns the gene HLA-G and plasma cell myeloma.