While both SPHK2 and PPIF are overexpressed and likely contribute to neuronal death in both human patients with Huntington’s disease or Alzheimer’s disease and rodent models of these diseases, knockout or inhibition of these genes protects against neurodegeneration (Moruno-Manchon et al., 2017; Takasugi et al., 2011; Du et al., 2008; Du et al., 2011). The gene discussed is SPHK2; the disease is early-onset autosomal dominant Alzheimer disease.