TARDBP and amyotrophic lateral sclerosis: Amyotrophic lateral sclerosis (ALS) is a clinical diagnosis based on a history of progressive motor dysfunction that demonstrates a combination of upper motor neuron (UMN) and lower motor neuron (LMN) signs. The vast majority of ALS cases are pathologically characterized by the deposition of abnormal ubiquitinated inclusions immunoreactive to transactive response DNA-binding protein 43 (TDP-43). ALS with TDP-43 pathology features axonal phosphorylated TDP-43 (pTDP-43) aggregates predominantly located in the facial and hypoglossal nuclei and anterior horn cells.