The direct binding interface between DR6/APP was reported by Nikolov's group, which is formed by the first CRD module of DR6 and H1, H2 helices of APP‐E2 domain.[24] This DR6/APP complex implies that targeting of the surface pocket in CRD1 of DR6 by exogenous chemicals may restraint the activation of necroptosis pathway to prevent tumor metastasis. The gene discussed is APP; the disease is neoplasm.