The interaction between lipids and metal ions is important for metal sensing, cellular signal transduction, and oxidative lipid damage. While most previous work overlooked the phosphate group of lipids for metal binding, we herein highlight its importance. Phosphocholine (PC) and its headgroup inversed choline phosphate (CP) lipids were used to prepare liposomes. From dynamic light scattering (DLS), Zn causes significant aggregation or fusion of the CP liposomes, but not PC liposomes. The size change induced by Zn is not fully reversed by adding EDTA, implying liposome fusion induced by Zn. Isothermal titration calorimetry (ITC) shows that binding between Zn and CP liposomes is endothermic with a K of 110 μM Zn, suggesting an entropy driven reaction likely due to the release of bound water. In comparison, no heat was detected by titrating Zn into PC liposomes or Ca into CP liposomes. Furthermore, Zn causes a transient leakage of the CP liposomes, and further leakage is observed upon removing Zn by EDTA. Transmission electron microscopy (TEM) with negative stained samples showed multilamellar CP lipid structures attributable to Zn sandwiched between lipid bilayers, leading to a proposed reaction mechanism. This work provides an interesting system for studying metal interacting with terminal phosphate groups in liposomes, affecting the size, charge, and membrane integrity of the liposomes.