Collectively, these experiments show that intracellular clusters of Caspase-8, RIPK1, RIPK3, and MLKL are readily detectable under idealized cell culture conditions, that elevated necroptotic signaling occurs in a subset of IBD, and that cytoplasmic clustering of Caspase-8 correlated with necroptotic signaling across a set of biopsies from two patients with IBD. This evidence concerns the gene RIPK1 and inflammatory bowel disease.