Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells via engagement of its cognate receptor, death receptor 5 (DR5).1 However, a significant number of cancer cells are resistant to TRAIL; particularly some highly malignant cancers such as melanoma and pancreatic cancer.2,3 Several novel drugs targeting TRAIL receptors are currently in clinical trials,4 though TRAIL resistance limits their effectiveness. The gene discussed is TNFSF10; the disease is familial pancreatic carcinoma.