While the early studies showed that the effect of imipridones on tumor cells occurs through inducing the expression of TRAIL and its receptor DR5 [3,7], as well as increasing the sensitivity of cells to exogenous TRAIL [8], recent observations demonstrated mitochondrial caseinolytic serine protease ClpXP, localized within the mitochondrial matrix as the only intracellular target for imipridones [2,9,10]. Here, TNFSF10 is linked to neoplasm.