TNFSF10/TRAIL (tumor necrosis factor superfamily member 10) is a typical death ligand expressed on natural killer cells and cytotoxic T lymphocytes. This protein preferentially induces apoptosis in transformed and tumor cells, but does not appear to kill normal cells although it is expressed at a significant level in most normal tissues. TNFSF10 induces apoptotic cell death in cancer by binding to its functional death receptors, death receptor (DR) 4 (TNFRSF10A/TRAIL-R1) and DR5 (TNFRSF10B/TRAIL-R2) to activate the extrinsic apoptosis pathway. TRAIL also activates c-Jun N-terminal kinase (MAPK8/JNK) and the transcription factor nuclear factor-κB (NFκB). The binding of this protein to its receptors has been shown to trigger the activation of MAPK8/JNK, caspase 8, and caspase 3.