Protection by the intact NOD2–RIPK2 pathway against experimental IBD required polyubiquitination of RIPK2 as MDP activation of NOD2 did not ameliorate DSS-induced colitis in mice deficient in cIAP2 or Pollino3, the E3 ligases for K63-linked polyubiquitination of RIPK2 (Bertrand et al., 2009; Yang et al., 2013). This evidence concerns the gene NOD2 and inflammatory bowel disease.