As haploinsufficiency of DPY30 increases severity of the spastin-HSP phenotype by reducing age at onset, the rescue of spastin-depletion-induced lysosomal enlargement (although not lysosomal ultrastructural abnormalities) by depletion of DPY30 is at first sight counter-intuitive. The gene discussed is DPY30; the disease is hereditary spastic paraplegia.