Diablo homolog (DIABLO) is a mitochondrial protein encoded by the DIABLO gene. SMAC is a mitochondrial protein that promotes cytochrome c- and TNF receptor-dependent activation of apoptosis by inhibiting the effect of IAP–a protein that negatively regulates apoptosis, or programmed cell death. SMAC is normally a mitochondrial protein localized to the mitochondrial intermembrane space, but it enters the cytosol when cells undergo apoptosis. Through the intrinsic pathway of apoptosis, BCL-2 proteins like BAK and BAX form a pore in the outer mitochondrial membrane, leading to mitochondrial membrane permeabilization and the release of both cytochrome c and SMAC. While cytochrome c directly activates APAF1 and caspase 9, SMAC binds IAPs, such as XIAP and cIAP proteins, to inhibit their caspase-binding activity and allow for caspase activation of apoptosis. SMAC is ubiquitously expressed in many cell types, implicating it in various biological processes involving apoptosis. Currently, nonapoptotic functions for SMAC remain unclear.