The intrinsic mitochondrial pathway of ceramide-assisted apoptosis is largely regulated by caspases and Bcl-2 family members. Crosstalk between signaling members is designated by arrows. Loss of mitochondrial outer membrane permeability (MOMP) subsequently leads to the release of proapoptotic proteins: cytochrome c, apoptosis-inducing factor (AIF), and second mitochondria-derived activator of caspase (SMAC)–direct inhibitor of apoptosis protein (IAP)-binding protein with low PI (DIABLO). GSK3β, glycogen synthase kinase 3β; HRK, harakiri; JNK, JUN N-terminal kinase; PKC, protein kinase C; PP2A, protein phosphatase 2A; TXNIP, thioredoxin interacting protein.