In order to investigate the causes driving pathological TDP-43 phosphorylation, we have developed a C. elegans model of TDP-43 proteinopathy exhibiting TDP-43 phosphorylation dependent neurodegeneration and neurotoxicity; in C. elegans, phosphorylation of TDP-43 at serines 409 and 410 suffices to promote TDP-43 mediated neurotoxicity [14]. Here, TARDBP is linked to proteostasis deficiencies.