Recent in vitro studies have demonstrated that within the LCD of TDP-43, a balance between hydrophobic and electrostatic forces results in a conserved α-helical structure that is required for induction of liquid-liquid phase separation; interestingly, ALS mutations within this region significantly disrupt phase separation and promote the conversion to aggregates (Conicella et al., 2016; Li et al., 2018). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.