Our research group investigates cellular mechanisms underlying inherited neurological disorders, with an emphasis on neuromuscular and movement disorders. In particular, the pathogenesis of hereditary spastic paraplegias, which affect corticospinal motor axons in a length-dependent manner, is an area of very active interest. These disorders comprise over 70 distinct genetic loci, with 20 genes identified whose proteins segregate into a few common cellular themes. In addition to an active clinical program assessing new patients with these disorders, we investigate the functions of the disease gene products at the cellular level and in animal models. We have identified that the most common forms of inherited spastic paraplegia are due to mutations in genes encoding proteins with hydrophobic hairpin domains that help shape the distinct morphology of the tubular endoplasmic reticulum network. A number of these proteins as well as other spastic paraplegia proteins implicated in endocytic processes also act as inhibitors of bone morphogenetic protein signaling, providing an exciting translational line of investigation. Our current studies investigate both the disease pathogenic mechanisms as well as the more fundamental aspects of how organelles are shaped in cells, and why this is particularly important for neurons. The common pathogenic themes that are emerging will likely represent novel targets for therapeutic intervention.