Glycosphingolipids (GSLs) are synthesized by the stepwise addition of sugars first to ceramide and then to the growing glycans. Shown as examples are major brain GSLs. Ceramide (Cer) is the acceptor for UDP-Gal:ceramide β-galactosyltransferase or UDP-Glc:ceramide β-glucosyltransferase in the major pathways to biosynthesis of the quantitatively major GSLs in oligodendrocytes (shaded pink) and nerve cells (shaded blue), respectively. GalCer is the acceptor for GalCer sulfotransferase, which adds a sulfate group to the C-3 of galactose to form sulfatide. Extension of GlcCer to the major brain gangliosides occurs by the action of UDP-Gal:GlcCer β1-4 galactosyltransferase to make lactosylceramide (LacCer) and then CMP-Neu5Ac:lactosylceramide α2-3 sialyltransferase to make the simple ganglioside GM3. GM3 is a branch point and acts as the acceptor for UDP-GalNAc:GM3/GD3 β1-4 N-acetylgalactosaminyltransferase to generate a-series gangliosides and for CMP-Neu5Ac:GM3 α2-8 sialyltransferase to generate GD3 and the b-series gangliosides. Similarly, the action of an α2-8 sialyltransferase on GD3 gives rise to GT3 and the c-series gangliosides. Enzymes for subsequent elongation are common to the a-, b-, and c-series gangliosides.