Most human GPI anchors are thought to contain three mannose residues, while most yeast GPI anchors contain four. Recently, a human homologue of the yeast enzyme responsible for addition of the fourth mannose residue to GPI molecules was identified and shown to mediate synthesis of human GPI molecules with four mannose residues. While the mannose donor and the nature of the bond linking the third and fourth mannose residues have not been established directly in studies with the human enzyme, these features are known for yeast and the normal human gene restores GPI synthesis in mutant yeast. This observation, tegether with the sequence similarities between human PIGZ and and Saccharomyces cerevisiae smp3,supports the inference that the human enzyme uses dolichol-P-mannose as a donor. The functional distinction between GPI anchors with three and four mannose residues is unknown, although the latter appear to be abundant in many human tissues (Taron et al. 2004).