This result implies a mistargeting of S1PR1 in acid sphingomyelinase deficiency and Niemann-Pick disease, which is akin to other proteins aberrantly mislocalized away from the plasma membrane in these diseases, such as Met receptor tyrosine kinase or K-Ras (Schuchman and Wasserstein, 2016; Praggastis et al., 2015). This evidence concerns the gene S1PR1 and acid sphingomyelinase deficiency.