Human SND2 mediates ER targeting of GPI?anchored proteins with low hydrophobic GPI attachment signals

Over 100 glycosylphosphatidylinositol-anchored proteins (GPI-APs) are encoded in the mammalian genome. It is not well understood how these targeted and translocated to endoplasmic reticulum (ER). Here, we reveal that many GPI-APs, such as CD59, CD55, CD109, utilize human SND2 (hSND2)-dependent ER targeting machinery. We also found signal recognition particle receptors seem cooperate with hSND2 target GPI-APs ER. Both N-terminal sequence C-terminal GPI attachment of contribute via hSND2-dependent pathway. Particularly, hydrophobicity acts determinant dependency. Our results explain route mechanism cells.