TNF and cyst: The rationale of Smac mimicry in ADPKD therapy relies on the fact that the cystic fluid of ADPKD cysts (in both the Pkd1−/− mouse and ADPKD patients) contains high amounts of TNF-α and the cells lining the cyst also overexpress the TNF-α receptor 1, which activates TNF-α signaling [280,281].