The cell biology of neuronal ceroid lipofuscinosis

Neuronal ceroid lipofuscinosis (NCL) defines a group of neurodegenerative diseases that are characterized by the accumulation of autofluorescent pigment within lysosomes. Mutations in at least 12 different human genes (the list is still growing) give rise to distinct NCL variants. While in some cases, the underlying mutations arise in genes with established roles in lysosome function (cathepsin D for example), the functions of the proteins encoded by most NCL genes remain unknown. We are thus taking advantage of the wealth of human genetic information concerning neuronal ceroid lipofuscinois to advance understanding of the specific roles played by NCL proteins in supporting lysosome function. We anticipate that an improved understanding of the cellular functions of NCL proteins will lead to new therapeutic strategies for the treatment of these diseases.