TARDBP and amyotrophic lateral sclerosis: The mechanism of transition of physiological nuclear TDP-43 to pathologic, irreversible and insoluble protein assemblies remains enigmatic, but it is likely triggered by the proteolytic release of its C-terminal LCD, which harbors most of the ALS-linked mutations1 and possesses high propensity to self-associate11, 29, phase separate12, 13, and aggregate2.