The autophagy-lysosomal pathway has been well-established to be crucial in PD pathogenesis, especially the lysosomal sphingolipid metabolism pathway, which includes well established PD-associated genes including GBA1, GALC, SMPD1 and others.53,54 SPNS1 deficiency results in lipid accumulation in the lysosome and impaired lysosomal function.28 This evidence concerns the gene SMPD1 and Parkinson disease.