Mice with the intestinal epithelial cell (IEC)-specific deletion of caspase-8 or its adapter FADD develop colitis and ileitis with a loss of Paneth cells and these effects are rescued by RIPK3 deficiency, underlying the importance of necroptosis in driving the pathology in both the small and large intestine [62,63]. Here, CASP8 is linked to Crohn ileitis.