In the study by Juan Tang et al. [31], RNF125 is a kind of additional E3 ubiquitin ligase initiating NLRP3 LRR domain ubiquitination linked by K63, and the continuous NLRP3 ubiquitination by RNF125 and Cbl-b makes inflammasome less activated and restricts the endotoxemia. Here, NLRP3 is linked to serum lipopolysaccharide activity.