NOD2 and Crohn's disease: loss or gain of function?

The human nucleotide binding and oligomerization domain (NOD)-containing protein family consists of some 25 members related to the Apaf-1/Ced-4 family of apoptosis regulators and certain plant disease-resistance genes (Inohara et al., 2004). One member, NOD2 (CARD15), has gained recent prominence through its association with increased susceptibility to several clinically important human inflammatory diseases, especially Crohn's disease (CD). NOD2 is a cytoplasmic molecule involved in sensing microbial cell wall components and regulating inflammatory processes and apoptosis. This review focuses on recent insights into the functions of normal and variant NOD2 proteins and the pathogenetic mechanisms underlying NOD2-associated inflammatory diseases.