PRKN and Alzheimer disease: Based on the multi-faceted roles that mitophagy plays in AD pathogenesis (Salminen et al., 2013), we integrate various overwhelming evidence ranging from cellular models to clinical patients that autophagic and mitophagic dysfunction result from ApoE4—multiple interferences of general autophagic processes, fission inhibition, fusion-related protein accumulation, PINK1/Parkin signaling blockage—and highlight additional findings that helps to further elucidate the cross talk of ApoE4 and its effector, as well as the regulations of mitochondrial dynamics events.