Niemann-Pick disease type C (NPC) is an inherited lysosomal storage disorder characterized by cholesterol and sphingolipid accumulation, leading to complex progressive neurodegeneration and death. The S1P/S1PR axis is a ligand/receptor combination involved in NPC pathology, and the binding of extracellular S1P to S1PR activates a pro-survival intracellular signaling pathway unique to each S1PR isoform, providing potential therapeutic targets. FTY720 is a high-affinity ligand agonist of S1PR1 and has been shown to decrease cholesterol and glycosphingolipid levels in NPC1 mutant fibroblasts as well as activate the synthesis of cytoprotective proteins through distinct pro-survival signaling pathways. However, it is unclear if FTY720 activates these pro-survival pathways in NPC knockout cells. Current therapies for NPC disease have shown the involvement of the S1P/S1PR axis in alleviating symptoms of NPC models. However, current treatment effects are suboptimal, underscoring the need for additional therapeutic options. Preliminary data confirms significantly increased cell death in HeLa NPC KO compared to WT (p = 0.0028) and treatment of HeLa KO NPC cells with 2 uM FTY720 did not significantly reduce cell death. A dose escalation study will be performed with increasing concentrations of FTY720. Additionally, western blot analyses will be conducted to examine the pro-survival proteins AKT and MEK, which are modulated by the S1P/S1PR axis. Understanding FTY720's role in pro-survival signaling pathways of S1PRs could lead to significant developments in new therapeutic approaches to treating NPC disease and other neurodegenerative diseases.