TARDBP and amyotrophic lateral sclerosis: Moreover, the DNA of the autoregulatory region that codifies the TARDBP 3’untranslated regions (3’UTR) is demethylated which is associated with reduced alternative splicing, increased levels of TARDBP mRNA, and in the end, augmenting the levels of cytoplasmic TDP-43 protein in affected neurons in ALS (Figure 1A) (Koike et al., 2021).