Two decades ago, a newly described gene called Nucleotide-binding Oligomerization Domain-containing 2 (NOD2, formerly known as Caspase Recruitment Domain 15 or CARD15), initially associated with susceptibility to Crohn’s disease [9–11] and Blau syndrome [12], was shown to mediate recognition of bacterial peptidoglycan (PGN) [13,14]. Here, NOD2 is linked to Crohn disease.