Taken together, this investigation provides further validation that the partial depletion of SRSF1 is a promising gene therapy approach for neuroprotection, showing minimal effects of SRSF1 depletion on the splicing and nuclear export of cellular transcripts in either healthy or C9ORF72-ALS neurons at a global genome-wide level. Here, SRSF1 is linked to amyotrophic lateral sclerosis.