I am exploring whether the ER stress transcription factor XBP1s can alleviate cellular, biochemical and behavioral phenotypes associated with TDP-43 toxicity upon targeted expression to brain neurons and elucidate how these two proteins interact with each other to elicit pro-survival or pro-apoptotic outcomes. To do so I will perform biochemical, cellular, histological, and behavioral studies to assess the extent of mXBP1s protection. Thus, at the end of this work, it might be possible to rationally target XBP1s signaling to resolve TDP-43-mediated ER stress in a manner that was not previously conceivable.