ALS, amyotrophic lateral sclerosis; APP, amyloid precursor protein; TARDBP, transactive response DNA-binding protein gene;  TDP-43, Transactive response DNA-binding protein 43; CTD, C-terminal domain (CTD); NTD, N-terminal domain; NLS, nuclear localization signal; fALS, familial amyotrophic lateral sclerosis; sALS sporatic amyotrophic lateral sclerosis; RRMI and RRM2, RNA recognition motifs 1 and 2, respectively.