TARDBP and proteostasis deficiencies: The phosphorylated-tau/total-tau (pTau:tTau) ratio in cerebrospinal fluid (CSF) is markedly reduced in ALS/FTD spectrum disorders, including TDP-43 proteinopathies, compared to other neurodegenerative diseases, with intermediate reductions in 4R tauopathies like progressive supranuclear palsy and corticobasal degeneration.