TARDBP and amyotrophic lateral sclerosis: This is the first mechanism‐focused and cell‐based drug discovery study that lays the foundation for studies that will identify compounds based on their ability to restore neuron health, and also reports NU‐9 as the first compound that eliminates UMN degeneration that occurs due to mSOD1 toxicity and TDP‐43 pathology, an important step in drug discovery efforts for ALS, HSP, PLS, and ALS/FTLD patients.