Since strategies to modify SPL activity are being explored in both pre-clinical and clinical trials of several conditions, including MS and rheumatoid arthritis, further characterization of SPL inhibition in pre-clinical disease models together with transgenic mouse approaches with a CNS focus will provide new insights into the development of new S1P-based therapies for the therapeutic benefits of neurodegenerative diseases. This evidence concerns the gene SGPL1 and neurodegenerative disease.