The fact that the majority of FTD/ALS-causing pathogenic mutations in the TDP-43 gene (TARDBP) either introduce or disrupt potential serine/threonine phosphorylation sites or introduce phosphomimic residues (glutamate/aspartate) [2] strongly suggests that alterations in the phosphorylation status of TDP-43 play a key role in TDP-43 pathogenesis and might contribute to biochemical heterogeneity of TDP-43 aggregates. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.