Previous studies have shown that OTUD4 is a K63 deubiquitination enzyme that interacts with MYD88, reduces the K63‐linked poly‐Ub levels of MYD88, and activates the MYD88‐dependent signal transduction.[22, 23] In addition, the activation of the MYD88/NF‐κB signaling pathway was involved in the progression of IBD.[24, 25] Therefore, we hypothesized that the SPARC/OTUD4 axis may activate the MYD88/NF‐κB signaling pathway in a K63‐polyUb‐dependent manner. Here, MYD88 is linked to inflammatory bowel disease.