Lysosomal storage disorders (LSDs) are a group of inherited diseases caused by defects in lysosomal enzymes, transporters, or associated proteins, leading to substrate accumulation and progressive cellular dysfunction.[1] Many LSDs involve the central nervous system and cause neurodevelopmental impairment, neurodegeneration, or both, making them relevant to NeuroWiki's mechanistic disease graph.[1:1][2]
Neurons are especially vulnerable to lysosomal failure because they depend on efficient long-lived protein and organelle turnover. Across neurodegenerative LSDs, recurring themes include impaired autophagy, disturbed lipid handling, mitochondrial dysfunction, and synaptic failure.[1:2][2:1]
Unifying biology of neurodegeneration in lysosomal storage diseases. Journal of Inherited Metabolic Disease (2025). ↩︎ ↩︎ ↩︎
Addressing neurodegeneration in lysosomal storage disorders: Advances in Niemann Pick diseases. Neuropharmacology (2020). ↩︎ ↩︎