Lipid rafts are discrete microdomains found in cell membranes that contain lipids with predominantly saturated hydrocarbon chains. Lipids found include but are not limited to cholesterol, glycosphingolipids such as gangliosides, and proteins modified with glycosylphosphatidylinositol (GPI) anchors. Given that cholesterol is a major component of lipid rafts, its extraction or sequestration by the drugs methyl-beta-cyclodextrin (MβCD) and filipin, respectively, is commonly used to disrupt rafts. Since cholesterol can be synthesized de novo by cells, long term disruption of lipid rafts often includes treatment with the statin mevinolin, a potent inhibitor of the rate-limiting enzyme in cholesterol production, as well as mevalonic acid, a precursor to isoprenoids essential for cellular survival. In previous work we found that exposure of murine neuroblastoma cells (N2a) to either MβCD or filipin followed by a 12h incubation with mevinolin and mevalonic acid resulted in disruption of lipid rafts while maintaining cell viability. Interestingly, disruption of lipid rafts by MβCD led to changes in the ganglioside content of N2a cells; the most notable change being in the monosialoganglioside GM1. While GM1 is found predominantly at the cell surface, disruption of lipid rafts resulted in a marked increase in the presence of GM1 on the nuclear envelope. Signaling through GM1 is important in many cell types, particularly neurons, and GM1 localized to the nuclear membrane has been shown to affect calcium release. Taken together, the effects of lipid raft disruption seen in N2a cells permits the hypothesis that the long term (12h) effects of the drugs MβCD, mevinolin and mevalonic acid on N2a cells initiates cellular differentiation and changes in ganglioside content. This work studied the effects of MβCD disruption of lipid rafts on N2a cell morphology as well as content and subcellular localization of the ganglioside GM1 in N2a cells.