Covalent attachment of glycosylphosphatidylinositols (GPIs) to the protein C-terminus is one of the most common posttranslational modifications in eukaryotic cells. In addition to anchoring surface proteins to the cell membrane, GPIs also have many other important biological functions, determined by their unique structure and property. This account has reviewed the recent progress made in disclosing GPI and GPI-anchored protein biosynthesis, in the chemical and chemoenzymatic synthesis of GPIs and GPI-anchored proteins, and in understanding the conformation, organization, and distribution of GPIs in the lipid membrane.
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