Comparison between human and fly TDP43. (a) Schematic representation of each domain (and amino acid position) in the two orthologs. (b) Alignment of the human (TDP-43) and fly (TBPH) proteins. The longest isoforms of human and fly proteins were used for this analysis (Uniprot accession no. Q13148 and O97468, resp.). Amino acids identical (∣) or similar (:) between the two proteins are indicated. Bold residues indicate the RNA recognition domains, RRM1 and RRM2. The RNP consensus sequences present in each RRM are highlighted (bold and underlined). All potential phosphorylation sites within human TDP-43 are indicated by asterisks. Importantly different studies have found a strong link between hyperphosphorylation at Serine379, Serine403, Serine404, Serine409, Serine410, and the inclusions of TDP-43 in FTLD-U/ALS [28–34].