Toll-like receptor (TLR) pathways play a pivotal role during the pathogenesis of inflammatory diseases including ulcerative colitis (UC) by recognizing pathogen-associated molecular patterns and consequently inducing proinflammatory signals. Pellino-1 is an E3 ubiquitin ligase and contributes to the innate immune response through the interaction with key signaling molecules including MyD88 and RIP kinases upon the receptor engagement. Mice deficient for Pellino-1 were viable and healthy, but completely protected from a septic shock when challenged with the lethal dose of lipopolysaccharide (LPS).