KO of S1R accelerates the onset and progression of ALS in the SOD1G93A mouse model of ALS (Mavlyutov et al., 2013), whereas the S1R agonists PRE-084 and SA4503 are neuroprotective and extend survival of SOD1G93A mice (Mancuso et al., 2012; Ono et al., 2014). This evidence concerns the gene TMBIM4 and amyotrophic lateral sclerosis.