The α,β2,μ2,σ2 heterotetrameric AP2 complex is recruited exclusively to the phosphatidylinositol-4,5-bisphosphate (PtdIns4,5P2)-rich plasma membrane where, amongst other roles, it selects motif-containing cargo proteins for incorporation into clathrin-coated vesicles. Unphosphorylated and μ2Thr156-monophosphorylated AP2 mutated in their αPtdIns4,5P2, μ2PtdIns4,5P2, and μ2Yxxϕ binding sites were produced, and their interactions with membranes of different phospholipid and cargo composition were measured by surface plasmon resonance. We demonstrate that recognition of Yxxϕ and acidic dileucine motifs is dependent on corecognition with PtdIns4,5P2, explaining the selective recruitment of AP2 to the plasma membrane. The interaction of AP2 with PtdIns4,5P2/Yxxϕ-containing membranes is two step: initial recruitment via the αPtdIns4,5P2 site and then stabilization through the binding of μ2Yxxϕ and μ2PtdIns4,5P2 sites to their ligands. The second step is facilitated by a conformational change favored by μ2Thr156 phosphorylation. The binding of AP2 to acidic-dileucine motifs occurs at a different site from Yxxϕ binding and is not enhanced by μ2Thr156 phosphorylation.