Proc. Natl. Acad. Sci. USA. 106: 17711-17716 (2009)

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) play various roles in cell-cell and cell-environment interactions. GPI is synthesized in the endoplasmic reticulum (ER) from phosphatidylinositol (PI). Cellular PI contains mostly diacyl glycerol whereas mammalian GPI-APs have mainly 1-alkyl-2-acyl PI. This characteristic is the result of diacyl to alkyl-acyl change occurring during GPI biosynthesis. Here, we demonstrated that generation of alkyl-containing GPI is dependent upon the peroxisomal pathway. The result highlights cooperation of three organelles, the ER, the Golgi and the peroxisome, in the generation of the lipid portion of GPI-APs.