Lysosomal deficiencies that may lead to neurodegeneration. Functions of lysosomes are regulated at multiple levels, including coordinated transcriptional regulation of lysosomal genes, trafficking of lysosomal proteins to the lysosomes, and proper function of the lysosomal membrane proteins and luminal acid hydrolases. Deficiencies of any of these processes may lead to deficiencies of reduced lysosomal degradation of aged or toxic proteins. The lysosomal substrate accumulation may in turn result in lysosomal expansion and storage and further disruption of its activities. Accumulation of aged, toxic or aggregated proteins and organelles, and accumulation of autophagosomes may lead to eventual neurodegeneration.