When we investigated the impact of SUMOylation on TDP-43 splicing activity, we first found that the TDP-43 K136R mutant, whose folding and structure are similar to the wild-type protein, maintained the RNA-binding activity towards its targets although it was slightly decreased compared to the wild-type protein and to the mutant TDP-43 harbouring ALS-associated mutations in the C-terminal domain. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.