GSLs

Glycosphingolipids (GSLs) are a diverse class of lipid molecules found predominantly in the outer leaflet of animal cell membranes. Each GSL comprises a ceramide backbone linked to one or more sugar residues; the glycan headgroup determines the class and function. The ceramide consists of a sphingosine base amide-linked to a fatty acid, while the sugar moiety can range from a single sugar to complex oligosaccharides.

GSLs are commonly divided into neutral and acidic species. Neutral GSLs include cerebrosides (glucosylceramide and galactosylceramide) and globosides, which contain neutral sugar chains. Acidic GSLs include gangliosides, which bear one or more sialic acid residues, and sulfatides, which feature sulfate groups. Globally, gangliosides are particularly abundant in the nervous system, where they participate in cell recognition and signaling. The blood group antigens A, B, and O are expressed in part by specific glycosphingolipid structures on red blood cells and tissues.

Biosynthesis occurs in the Golgi apparatus, starting from ceramide synthesized in the endoplasmic reticulum; glycosyltransferases add sugars stepwise to form the mature glycan headgroup. Lysosomal degradation by specific glycosidases recycles GSLs; defects in these enzymes cause lysosomal storage diseases, such as Gaucher disease (glucosylceramide accumulation) and GM1 gangliosidosis.

Functions of GSLs include contributions to membrane microdomains, receptor activity, and mediating cell–cell and host–pathogen interactions. Some GSLs act as receptors for bacterial toxins (for example, GM1 for cholera toxin). In clinical and research contexts, GSLs serve as biomarkers and therapeutic targets in neurology and oncology.