NPC1 and lysosomal storage disease: For instance, deficiencies in acid sphingomyelinase (catalyzing lysosomal SM hydrolysis) and NPC1 and CLN3 (lysosomal lipid or lipid-derived metabolite transporters) cause pathologic accumulation of lysosomal storage materials and present clinically as lysosomal storage diseases with early-onset and fatal neurodegeneration (29).