However, the fact that they may be acting as a cytoplasmic protein “sink” to trap the predominantly nuclear TDP-43 has suggested that the onset of neurodegenerative diseases might be the consequence of the progressive nuclear loss of function of TDP-43 trapped within the cytoplasmic inclusions (this does not rule out, of course, that various “gain-of-function” mechanisms may be playing a role in parallel) [22]. Here, TARDBP is linked to neurodegenerative disease.