The exact mechanism by which mutant forms of TDP-43 affect its degradation is not clear, but there is evidence to suggest that ALS-associated mutations in TARDBP, most of which reside in the disordered prion-like domain, promote protein misfolding and stabilize TDP-43 within cytoplasmic inclusions (Kabashi et al. 2010; Johnson et al. 2009). Here, TARDBP is linked to amyotrophic lateral sclerosis.