In a recent study published in Science, Baughn et al. revealed that TDP-43 acts as a steric block in STMN2 pre-mRNA processing preventing inclusion of a deleterious cryptic exon, and present strategies for substituting this function to compensate for the loss of nuclear TDP-43 in a variety of neurodegenerative diseases (NDs) including amyotrophic lateral sclerosis (ALS).1 The gene discussed is STMN2; the disease is amyotrophic lateral sclerosis.