When lysosomal function declines, specific proteins, including tau, α-synuclein, and transactive response DNA binding protein of 43 (TDP-43), can accumulate within nerve cells, contributing to the onset of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). The gene discussed is MAPT; the disease is amyotrophic lateral sclerosis.