TARDBP and proteostasis deficiencies: This provided the first molecular evidence to explain the comorbidity that is common to ALS and FTLD (Lomen-Hoerth et al., 2002) and also led several groups to propose that ALS and FTLD-U represent two ends of a spectrum of TDP-43-mediated neurodegenerative diseases that can collectively be referred to as TDP-43 proteinopathies (Liscic et al., 2008; Chen-Plotkin et al., 2010).