To determine the biological relevance of TDP-43-regulated APA, we studied its effects on microtubule affinity regulating kinase 3 (MARK3), a highly significant (P = 9.4 × 10–16) hit from APA analysis of ALS/FTD frontal cortex neuron nuclei containing or depleted of TDP-43. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.