Sphingolipid activator proteins: proteins with complex functions in lipid degradation and skin biogenesis

Sphingolipid activator proteins (SAPs or saposins) are essential cofactors for the lysosomal degradation of membrane-anchored sphingolipids, Four of t he five known proteins of this class, SAPs A-D, derive from a single precur sor protein and show high homology, whereas the fifth protein, GM2AP, is la rger and displays a different secondary structure. Although the main functi on of all five proteins is assumed to lie in the activation of lipid degrad ation, their specificities and modes of action seem to differ considerably. It has recently been demonstrated that the action of the proteins is highl y enhanced by the presence of acidic lipids in the target membranes. These results have some interesting implications for the topology of lysosomal de gradation of lipids and may provide new insights into the function of these interesting proteins, which are ubiquitously expressed in the different ti ssues of the body. Recent studies indicated that the SAPs play an important role in the biogen esis of the epidermal water barrier, which has been demonstrated by the ana lysis of the skin phenotype displayed by SAP-knockout mice. The results obt ained so far have led to some new insights into the formation of the epider mal water permeability barrier and may lead to a better understanding of th is complex process.