TARDBP and amyotrophic lateral sclerosis: In analogy, the observed reduction, rather than increase in TDP-43 neurotoxic activity by ALS/FTLD-linked mutations (this study) – possibly reflecting reduction of inherent protein function – could consequently point to a loss-of-function mechanism by which depletion of TDP-43 function (e.g. via missense mutation, and/or truncation/aggregation, followed by cytosolic sequestration) would eventually lead to neuron loss [6], [7], [16].