Neuraminidases or sialidases are classified enzymes hydrolases the sialic acid residues from the glycoconjugates. In vertebrates, so far four different neuraminidases have been identified having distinct roles besides degradation of glycoconjugates. Neuraminidases differ in subcellular locations where Neuraminidase 1 is mainly localized in lysosomes having crucial regulatory roles and forms a multienzyme complex with protective protein/cathepsin A and ß-galactosidase. Only Neu1 is recognized when its functions or a component from the complex they together forged are defected, resulting two severe lysosomal storage disorders, sialidosis and galactosialidosis. To shed light on these disorders, Neu1-/- mice model lacking the enzyme was generated. By addition of sialic acid residue to the structure of Glycosphingolipids (GSLs), complex sugars in the membrane surface that provide special properties to cell, gangliosides are generated that further processed into 0-, a-, -b, -c series. Since the function of Neu1 in Glycosphingolipid pathway is unclear, to investigate the role of Neu1in this pathway, Neu1-/- mice crossed with the mice lacking b-and c- series of gangliosides, the GD3S-/- mice are used to generate Neu1-/-GD3S-/- mice. Even though mice showed indifferent ganglioside profile with a thin layer chromatography, they displayed decreased apoptotic signals and ER-stress markers with RT-PCR. However, western blotting and immunohistochemical studies revealed severe cell death in the brain. Moreover severe behavioral deficits were observed with open field and rotarod tests. The effects of b- and c- series of gangliosides on double knock-out mice still require further research that might reveal important roles in terms of cell death mechanism.