The nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene has been consistently implicated in the pathogenesis of CD since it was first identified in 2001.1, 2, 3 NOD2 is a member of the evolutionarily conserved family of NOD-like receptors (NLRs) that provide intracellular surveillance through detecting cytoplasmic pathogen-associated molecular patterns.4, 5, 6 NOD2 belongs to the NLRC subfamily, containing 2 amino-terminal caspase activation and recruitment domains (CARDs).7 This evidence concerns the gene NOD2 and Cowden disease.