Although the molecular mechanism behind the reduction of S1P content is thought to be complex in the case of HD it may be in part due to the reduced levels of the S1P biosynthetic enzyme, sphingosine kinase-1 (SPHK1; Di Pardo et al., 2017a,b), whose activity is normally associated with cell survival (Le Stunff et al., 2002; Morozov et al., 2013). The gene discussed is SPHK1; the disease is Huntington disease.