Here we used CRISPR/Cas9 to delete endogenous S1R and evaluate functional effects of expression of hS1R with amyotrophic lateral sclerosis (ALS) (E102Q) and distal hereditary motor neuropathy (dHMN) (Δ31–50) causing mutations. The gene discussed is TMBIM4; the disease is amyotrophic lateral sclerosis.