TARDBP and amyotrophic lateral sclerosis: In addition to establishing a potential new diagnostic biomarker, our finding that loss of TDP-43 splicing repression occurs during the presymptomatic phase of disease provides a strong rationale for the development of therapeutic strategies to complement TDP-43 splicing repression deficits for ALS—for example, an AAV9 gene therapeutic strategy that expresses a splicing repressor, termed CTR36.