Interestingly, a recent study showed that proteasome inhibitors bortezomib and MG132 activated the canonical necroptotic pathway in RIPK3-expressing mouse fibroblasts and human leukemia cells without caspase-8 inhibition (44), confirming that inhibition of caspase-8 activity may not be essential for induction of necroptosis. The gene discussed is RIPK3; the disease is leukemia.