While treatment with TNF-α alone did not induce apoptosis in either Pkd1 wild-type or null MEK cells even at high concentration (due to the activation of NF-κB which inhibited the activity of caspase 8) (Fan et al., 2013a), treatment with TNF-α combined with the SMAC (second mitochondria-derived activator of caspases) mimetic induced apoptosis in primary cultures of mural epithelial cells from human ADPKD cysts and Pkd1 null MEK cells, suggesting that SMAC-mimetic induces TNF-α–dependent cell death (Fan et al., 2013a). The gene discussed is PKD1; the disease is autosomal dominant polycystic kidney disease.