CLN protein distribution and their link to autophagy defects in neuronal ceroid lipofuscinoses
Many CLN proteins reside in the lysosomal matrix (CLN1, 2, 5, 10, 13) or at the lysosomal membrane (CLN3, 7), while others localize to different cellular compartments such as the ER membrane (CLN6). Disease-causing mutations in some of the CLN proteins inhibit autophagosome maturation (dashed red lines) and block autophagic flux, but the underlying mechanisms are unknown. Mutated lysosomal hydrolases (CLN1, 2, 10, 13) are unable to degrade autophagic cargo, which subsequently accumulate and impair lysosomal function.