This study aimed to define the role of HOIL-1 cleavage and C-HOIL-1 in modulating gut inflammation.<h4>Methods</h4>To investigate the impact of HOIL-1 cleavage on intestinal inflammation, the global and myeloid-specific transgenic mouse models with uncleavable HOIL-1 (lacking C-HOIL-1) were established, and their disease phenotypes and immune profiles were characterized under DSS-induced colitis. This evidence concerns the gene RBCK1 and colitis.