Chang MC, et al. – Whether or not progranulin deficiency causes impairment of autophagy and transactive response DNA–binding protein of 43 kD (TDP–43) accumulation, has been examined in this study. Autophagy is implicated as a novel therapeutic target for GRN–associated neuronal ceroid lipofuscinosis (NCL) and frontotemporal dementia (FTD). Data outline the emerging theme of defective autophagy in the broader FTD/amyotrophic lateral sclerosis spectrum of neurodegenerative disease.