GPI-PLD (glycosylphosphatidylinositol- specific phospholipase D), a 815– amino acid protein, is expressed in numerous tissues and cells and specifically cleaves GPI-anchored proteins. Liver has the highest level of GPI-PLD expression and is the primary organ contributing to GPI-PLD in the serum. GPI-PLD is abundant in serum in which it associates with apolipoproteins AI and AIV. Increased serum GPI-PLD is associated with insulin resistance and elevated serum triglycerides. Many surface proteins are attached to eukaryotic cell membranes via glycosylphosphatidylinositol (GPI) anchors that are covalently bound to the C-terminus of the protein and cleavage of the GPI moiety by GPI-PLD, only enzyme known that cleavage GPI anchor, may represent a means of regulating attachment of these proteins to the cell surface, or alternatively, their release into the extracellular environment.