Its polyunsaturated acyl chains exclude it from GM1 lipid rafts.
[5][6] The multiple negative charges on PIP2 are thought to cluster proteins with positive charges residing in the plasma membrane leading to nanoscale clusters.
Increases in cholesterol overcome PIP2 binding and sequester PLD2 into GM1 lipid rafts away from its substrate phosphatidylcholine.
Efflux of cholesterol causes PLD2 to translocate to PIP2 domains where it is activated by substrate presentation.
The drug hydroxychloroquine blocks ACE2 interaction with PIP2 in multiple cell types shifting its localization.