NOD2 and Cowden disease: These data suggest that the intact NOD2–RIPK2 pathway functions as a critical regulator of mucosal host defense mechanisms against gut microbiota through the production of α-defensin, and that impaired activation of RIPK2 in the presence of CD-associated NOD2 mutations predisposes hosts to chronic inflammation due to bacterial overgrowth (Inohara et al., 2005; Kobayashi et al., 2005; Chen et al., 2009; Philpott et al., 2014).