A key mediator of the extrinsic apoptosis pathway mediator for typical apoptotic cascades as well as initiator of signaling cascade reactions of necroptosis, TNF-α is extensively involved in the development of multiple diseases, such as inflammatory bowel disease (IBD), spontaneous colitis129, alcoholic liver disease, and NAFL/NASH130; notably, NAFL/NASH has been proven to be triggered by CyPD-induced mPTP opening, consistent with caspase-3-initiated caspase-6 cleavage and consequent cyt c release. This evidence concerns the gene CASP3 and inflammatory bowel disease.