The classical example is Crohn’s Disease, where mutations in the leucine-rich repeat domain of CARD15(NOD2), involved in ligand binding, represent the greatest genetic risk factor for development of the disease (although CARD15 mutation is neither necessary nor sufficient for the occurrence of Crohn’s Disease).118,119,146 With the identification of NOD2 mutations (CARD15 gene) as a major risk factor, came the implication that the steady-state sensing of gut peptidoglycan by NOD2 is part of healthy gut barrier homeostasis. This evidence concerns the gene NOD2 and Crohn disease.