Smooth transport of cargo by the trafficking machinery is very important during development and synaptic transmission. Defective glycosylation of proteins and lipids disrupts development pathways and alters brain function (Freeze et al., 2012). COG deficient cells also display altered glycosphingolipid biosynthesis. Complex gangliosides are sialic acid containing glycosphingolipids synthesized sequentially, beginning with GM3 and then extended by glycosyltransferases to the more elaborate GM1 gangliosides. Biochemical studies revealed decreased levels of sphingomyelin and GM3 gangliosides in COG2 deficient CHO cells (Spessott et al., 2010a,b). Gangliosides are ubiquitously expressed, but in the brain the expression of gangliosides and their glycosyltransferases change dramatically during development, from an abundance in of the precursor GM3 to a greater abundance of GM1 (Yu et al., 1988; Kracun et al., 1991, 1992; Ngamukote et al., 2007). Therefore, altered glycosphingolipid biosynthesis could be another reason for the specific neurological manifestation in COG-related congenital disorders.