The lipid phosphatase domain aided the E protein in binding to the phospholipid membrane on the cell surface by phosphorylating PtdIns(3,4,5)P3. PTEN's phosphorylation status also influences its binding to the plasma membrane. PTEN is found in the cytoplasm and nucleus of the cell and can be secreted. PTEN is exportable by exosomes . PTEN can be transported to the cytoplasmic side of the plasma membrane under normal conditions. It can dephosphorylate PtdIns P3 to PtdIns(4,5)P2, thereby blocking the PI3K signaling pathway in the cell. Not only is PtdIns(4,5)P2 the result of PtdIns(3,4,5)P3 dephosphorylation by PTEN, but it is also a prerequisite for PTEN membrane binding . PTEN comprises three domains: an N-terminal phosphatase domain, a C2 domain, and a C-terminal tail region containing a PSD-95/Dlg/ZO-1 homology (PDZ) domain binding sequence and several phosphorylation sites . PTEN is activated to target the plasma membrane when its C-terminal tail residues are dephosphorylated. Then it exposes its surface cationic residues and fast electrostatic membrane interaction . Once attached to the plasma membrane, PTEN will bind to and dephosphorylate 3-phosphoinositides, the most important of which is PtdIns(3,4,5)P3, resulting in PTEN breakdown . The C-terminal region's phosphorylation/dephosphorylation works as an electrostatic switch regulating protein-membrane translocation . PTEN interacts with the membrane via many locations. However, only when PI(4,5)P2 binds to the N-terminal domain, a conformational shift and rise in -helicity occurs .