TARDBP and proteostasis deficiencies: This is mostly due to the presence of aberrant protein states (proteinopathy) of two essential RNA/DNA binding proteins TDP-43 and FUS (Fused in sarcoma) in affected neurons, including cytosolic translocation, truncation, phosphorylation, ubiquitination, and aggregates formation (Lagier-Tourenne et al., 2010; Da Cruz and Cleveland, 2011).