Proximal tubule apoptosis is a prominent feature of acute and chronic kidney disease. Intrinsic apoptosis is triggered by mitochondria damage. BCL2-associated X protein (BAX)/ BCL2-antagonist/killer (BAK) pores in the outer membrane of mitochondria will cause translocation of cytochrome c from the mitochondria to the cytosol to initiate the formation of the apoptosome consisting of caspase-9, Apaf1, and cytochrome-c. The apoptosome will activate executionary caspases such as caspase-3. Apoptosis will cause epithelial cell loss. Animal studies, analyzing BAX/BAK double KO, Caspase-9, and Caspase-3 KO mice or chemical caspase-inhibitors indicated the protective role of apoptosis from kidney disease development.