Based on previous findings that UNC13A expression is reduced due to mRNA instability from noncoding region SNPs and CE inclusion following nuclear loss of TDP-43 (Brown et al, 2022; Ma et al, 2022), our study focused on UNC13A among REST target genes, proposing that the pathway from RBP dysfunction to REST upregulation and ultimately to UNC13A suppression plays a crucial role in ALS pathophysiology. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.