Hyperphosphorylated TDP-43 aggregates were first identified in post-mortem tissue of familial and sporadic ALS patients (Arai et al., 2006; Neumann et al., 2006), and Ser403/404 and Ser409/410 are the major phosphorylation sites of insoluble TDP-43 in ALS/FTD. This evidence concerns the gene TARDBP and frontotemporal dementia.