Niemann-Pick Disease, Type C (NPC) is a fatal, genetic, neurodegenerative disorder with no FDA-approved therapy. As a result of the genetic defect, unesterified cholesterol and glycosphingolipids accumulate in the endo-lysosomal system. A hallmark of this disease includes progressive, cerebellar degeneration however the link between lipid accumulation and neuron death is not fully understood. In this work, we sought to determine altered proteins and lipids in NPC with a focus on the cerebellum. Utilizing standard flow chromatography and Jet Stream ESI technology, we identified differential proteins and lipids including those involved in phosphoinositide and fatty acid metabolism. This presentation will include a description of the analytical methodology and examples of altered proteins and lipids found in NPC.