TARDBP and amyotrophic lateral sclerosis: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative syndrome of the upper and lower motor neurons (and their wider cortical networks) characterised by relentlessly progressive skeletal muscle paralysis that ultimately leads to respiratory failure and death.1 The site of onset of clinical symptoms and their spread in ALS are non-random, but within a strikingly heterogeneous clinical syndrome that is currently unified by the postmortem identification of neuronal and glial cytoplasmic inclusions of Trans-Activating Response (TAR) DNA-Binding Protein-43 (TDP-43).