Apoptosis is related to many diseases and development. Caspase-9 plays a central role in cell death induced by a variety of apoptosis activators. Cytochrome c, after released from mitochondria, binds to Apaf-1, which forms an apoptosome that in turn binds to and activate procaspase-9. Activated caspase-9 cleaves and activates the effector caspases (caspase-3, -6 and -7), which are responsible for the proteolytic cleavage of many key proteins in apoptosis. The tumor suppressor putative HLA-DR-associated proteins (PHAPs) were recently identified as important regulators of mitochondrion apoptosis. PHAP appears to facilitate apoptosome-medicated caspase-9 activation and to stimulate the mitochondrial apoptotic pathway. PHAP was also shown to oppose both Ras- and Myc-medicated cell transformation.