The protein encoded by this gene is a lysosomal acid sphingomyelinase that converts sphingomyelin to ceramide. The encoded protein also has phospholipase C activity. Defects in this gene are a cause of Niemann-Pick disease type A (NPA) and Niemann-Pick disease type B (NPB). Multiple transcript variants encoding different isoforms have been identified. [From RefSeq]
To date, over 160 mutations distributed along the SMPD1 gene have been detected in patients with Niemann-Pick disease types A and B. The majority of mutations are missense; however, nonsense, splicing, small insertions or deletions have been reported. Four common mutations have been identified; three of these mutations (Leu304Pro, Arg498Leu and Phe333Serfs) account for about 95% of patients with NPD-A, and one recurrent mutation, Arg608del, is responsible for most cases of NPD-B of Ashkenazi Jewish origin.