We hypothesized that trehalose activates TFEB through a hitherto uncharacterized pathway, and set out to test this hypothesis using a prototypical model of aberrant intralysosomal storage represented by juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease; OMIM #204200), the most prevalent neurodegenerative disorder of childhood. This evidence concerns the gene TFEB and neuronal ceroid lipofuscinosis.