Background: Determinants of membrane protein dual topological orientation are not known. Results: Dual topological conformers of lactose permease co-exist in proportion to membrane phospholipid composition. Post-assembly changes in phospholipid composition alter the proportional amounts. Conclusion: Dual conformations of membrane proteins are determined during and post-assembly by lipid-protein interactions. Significance: A thermodynamic model explains the existence of multiple conformers of …