In conclusion, we demonstrated that oxysterol accumulation in APOE4 and AD promotes greater expression of ABCA1 and caveolin-1, which endocytoses and traps ABCA1 in lysosomes and induces a dysfunctional lysosomal state in which ABCA1 fails to recycle back to the plasma membrane. The gene discussed is ABCA1; the disease is Alzheimer disease.