We found that human neurons lacking atlastin-1 have altered ER morphology, increased endosomal tubulation suggesting an ETF defect and abnormal lysosomal proteolytic activity, supporting the idea that ER and lysosome functions are linked in neurons and that defects in lysosomal function may contribute to the pathogenesis of atlastin-1-HSP. The gene discussed is ATL1; the disease is hereditary spastic paraplegia.