TARDBP and proteostasis deficiencies: The histopathological hallmark of TDP-43 proteinopathy is the mislocalization and accumulation of hyperphosphorylated, ubiquitinated, and N-terminally truncated TDP-43 in neurons and glial cells.18,25 C-terminal domain fragments of TDP-43 exit the nucleus to form TDP-43 cytoplasmic inclusions.32 TDP-43 histopathology is classified into subtypes A-E based on inclusion morphology and subcellular distribution,33,34 and each subtype is associated with particular causal gene mutations or clinical syndromes.35,36