As a postdoctoral fellow in the lab of Jeffrey Rothstein, I am studying how alterations in the composition and function of the nuclear pore complex (NPC) contribute to neurodegenerative disease pathogenesis, specifically in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). The NPC critically governs multiple cellular processes including gene expression and the transport of macromolecules between the nucleus and cytoplasm. It is a large, highly organized protein complex consisting of multiple copies of ~30 different nucleoporin proteins. Although the majority of these nucleoporin molecules exist within this complex, a subset have additional roles within the nucleus or cytoplasm as individual proteins. While many studies in the field using artificial overexpression disease model systems have reported cytoplasmic accumulations of a small subset of these nucleoporins, there exists a critical need to evaluate whether or not these proteins are altered within the NPC structure itself. Using super resolution microcopy and human induced pluripotent stem cell-derived neurons, my work has now addressed this gap in knowledge in human neurons from patients with the most common genetic form of ALS. Moreover, I have identified the nucleoporin POM121 as the critical initiator of a pathological cascade impacting NPC composition, function and downstream neuronal survival. Collectively, my work advances our knowledge of human neuronal NPC biology in health and disease and identifies compositional changes to the NPC as an early event in ALS pathogenesis.