In the early stages of AD, Aβ can transiently induce the nuclear translocation of TFEB; however, over time, the decline in nuclear levels of TFEB and the sustained increase in LAMP1 (lysosomal-associated membrane protein 1) indicate that the cellular adaptive response to Aβ is limited, ultimately leading to lysosomal dysfunction. The gene discussed is LAMP1; the disease is Alzheimer disease.