The identification of nucleotide-binding oligomerization domain 2 (NOD2, GeneID: 64127), also known as caspase recruitment domain-containing protein 15 (CARD15) as the first susceptibility gene in CD in 2001 [5], [6] has provided significant new insights in the pathogenesis of IBD focusing on the genetic background of innate immune response and interaction with bacterial antigens [7], [8], [9], [10]. The gene discussed is NOD2; the disease is Cowden disease.