Structurally the glycolipid transfer protein (GLTP) fold differs from other proteins that recognize glycolipids, such as non-specific lipid transfer proteins and lysosomal lipid degradation assisting proteins, even though they act on the same class of lipids. Proteins with glycan binding domains, such as lectins and pulmonary surfactant proteins share no structural similarity with the GLTP family either. Currently the unique GLTP-fold specific for binding glycosphingolipids is found only in the founding member GLTP and the phosphoinositol 4-phosphate adapter protein 2, FAPP2. FAPP2 was originally characterized as a member eight of the pleckstrin homology domain-containing family A (PLEKHA8). This review summarizes what is structurally required by the glycosphingolipids in order for them to be transported by the GLTPs.