Although it is likely that multiple factors contribute to the onset and progression of ALS, one hallmark is the presence of trans-activation response DNA binding protein-43 (TDP-43)–positive extranuclear inclusions in the affected neurons, which is identified in 97% of all ALS cases (Scotter et al., 2015; Jeon et al., 2019). The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.