Nevertheless, as there is no evidence indicating that disease-causative mutations in the PLD impact on TDP-43’s capacity to bind to RNA [74] and RNAs are not found in TDP-43 aggregates in ALS/FTD post-mortem tissue [75], it is currently unclear whether RNA-binding of TDP-43 is disrupted and may subsequently contribute to proteinopathy and disease development. This evidence concerns the gene TARDBP and frontotemporal dementia.