OPTN and inflammatory bowel disease: Furthermore, our study provides a novel explanation for the hyperactivation of NLRP3 inflammasome during IBD: VANGL2 down-regulation hinders the K27-linked ubiquitination of NLRP3, decreases OPTN-mediated autophagic degradation of NLRP3, and results in overactivation of the NLRP3 inflammasome, thus promoting IBD progression.