The IR was the most prominent in the SFPQ transcript. The SFPQ protein exhibits a reduced nuclear abundance in VCP mutant cultures and binds extensively to its retained introns New changes inside TANK-binding kinase 1 (TBK1) cause abnormal splicing patterns in people with amyotrophic lateral sclerosis . The most prevalent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a GGGGCC (G 4 C 2 ) repeat expansion in the first intron of C9ORF72. The production of the dipeptide repeat protein is abolished and neurodegeneration is rescued by the CRISPR-mediated deletion of the C9ORF72 promoter in motor neurons of ALS/FTD patients .