In 2020, Tang et al. found that the E3 ubiquitin ligase Casitas-B-lineage lymphoma protein-b (Cbl-b) was essential for preventing endotoxemia induced by a sub-lethal dose of LPS in a caspase-11/NLRP3-dependent manner (Tang et al., 2020). Here, NLRP3 is linked to serum lipopolysaccharide activity.