The pathological hallmarks of ALS include the retention, reduced expression, and aggregate formation of proline-and glutamine-rich introns of splicing factors . The splicing program during early neural differentiation is characterized by increased intron retention (IR). it has also used SOD1 and FUS mutant MNs to identify aberrant IR events in independent RNAseq datasets. Mutations in the RNA-binding protein FUS cause amyotrophic lateral sclerosis (ALS), a neurodegenerative disease that is devastating. FUS autoregulatory and splicing factor networks are impaired by FUS ALS pathogenic mutations due to intron retention . Mutant FUS impedes the proper splicing of minor introns in mRNAs that encode proteins that are essential for the survival of motor neurons . As a transcriptional regulator, the SVA retrotransposon in the FUS promoter has been associated with ALS .