Since poly-PR and the dysregulation of TDP-43 independently up-regulate the expression of NEAT1_2 that is essential for the paraspeckle formation11 and probably for the induction of neurotoxicity (Figs. 3 and 7), it could be assumed that the dysregulation of TDP-43 also enhances the paraspeckle formation in ALS/FTD cases without C9ORF72 mutation. Here, TARDBP is linked to frontotemporal dementia.