The efficacy of the ER stress modulator, Sephin1, to protect motor neurons and modulate TDP-43 localization and its toxicity has been first evaluated in two in vitro models, glutamate intoxicated motor neurons and arsenite intoxicated human neuroblastoma cell line, SH-SY5Y, and then in two genetic ALS animal models, SOD1G93A transgenic mice and TDP-43G348C transgenic zebrafish embryos. The gene discussed is TARDBP; the disease is neuroblastoma.