Apaf-1 and NOD1 are members of a new family, which are involved in the regulation of apoptosis and immune response. Each of them contains a caspase recruitment domain (CARD) and a nucleotide-binding oligomerization domain (NOD). A third member in this family was recently identified and designated NOD2. NOD2 interacts with RICK via a homophilic CARD-CARD interaction. NOD2 activates NF-κB, which is regulated by its carboxy-terminal leucine-rich repeat domain that acts as an intracellular receptor for components of bacteria. The variants of NOD2, either a frameshift or a missense, were associated with Crohn’s disease that is a main type of chronic inflammatory bowel disease.