The most provocative findings in our study revealed that U snRNA misregulation was observed in several distinct contexts: cells with a decreased expression of TDP-43 (Fig 4B–D) and spinal cord tissue samples of ALS patients (Fig 5), but not in the affected brain regions of FTLD-TDP (Supporting Information Fig S5A and B). Here, TARDBP is linked to amyotrophic lateral sclerosis.