SMPD3 deficiency caused no SM storage and the phospholipidome in all tissues of smpd3−/− mice remained unimpaired, unlike the fatal lysosomal SM storage in the smpd1−/− mouse,14, 15 a mimicry of human Niemann–Pick disease (Figures 2a and h).14, 15. Here, SMPD3 is linked to Niemann-Pick disease.