Most intriguingly, intestinal epithelium-specific deletion of caspase 8 or its activator, Fadd, which are inhibitors of necroptosis, depletes Paneth cells.31, 32 This loss of Paneth cells is rescued by deletion of necroptosis mediator, Ripk3. Furthermore, RIPK3 is increased in the intestine of IBD patient samples.31 Thus, activation of necroptosis is likely to be one of the causes of pathological Paneth cell loss. Here, CASP8 is linked to inflammatory bowel disease.