Our review entails the latest research findings on ApoE’s functions and its impact on AD, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Huntington’s disease (HD), vascular dementia (VD), and multiple sclerosis (MS), thus providing a fresh and insightful perspective on unraveling the mechanisms underlying neurodegenerative diseases. This evidence concerns the gene APOE and neurodegenerative disease.