TARDBP and amyotrophic lateral sclerosis: Given that almost all patients with ALS have TDP-43 pathology, the recent breakthroughs revealing that TDP-43 dependent mis-splicing of mRNA plays a major role in disease pathogenesis provides a fresh injection of hope into the field, not only for the ability to better understand molecular mechanisms, but also for the transformative potential with regard to biomarker development and therapeutics, desperately needed for patients living with this fatal disease.