A lyso-platelet activating factor phospholipase C, originally suggested to be a neutral-sphingomyelinase, is located in the endoplasmic reticulum.

Recently a putative mammalian neutral-sphingomyelinase was cloned [Tomiuk et al. (1998) Proc. Natl. Acad. Sci. USA 95, 3638-3643; GenBank accession number AJ222801]. We have overexpressed this enzyme in cultured cells and demonstrate, using four different tagged constructs, that it is localized at the endoplasmic reticulum and not at the plasma membrane. This localization precludes a role for enzyme AJ222801 in the sphingomyelin cycle. Furthermore, a recent publication demonstrated that this enzyme has lyso-platelet activating factor (PAF) phospholipase C activity [Sawai et al. (1999) J. Biol. Chem. 274, 38131-38139]. Together, these data suggest a role for enzyme AJ222801 in the regulation of PAF metabolism.