Almost four decades after the identification of the AKT protein and understanding of its 23 role in cancer, barriers remain in the translation of AKT inhibitors for clinical applications. 24 Here we provide new molecular insight into the first step of AKT activation where AKT 25 binds to the plasma membrane and its orientation is stabilised in a bilayer with lateral 26 heterogeneity (Lo-Ld phase coexistence). We have applied molecular dynamic 27 simulations, and molecular and cell biology approaches, and demonstrate that AKT 28 recruitment to the membrane requires a second binding site in the AKT Pleckstrin 29 Homology domain that acts cooperatively with the known canonical binding site. Given 30 the precision with which we have identified the protein-lipid interactions, the study offers 31 new directions for AKT-targeted therapy and for testing small molecules to target these 32 specific amino acid-PIP molecular bonds.