Currently, lipid nanoparticles (LNPs) are among the most clinically advanced drug delivery systems in the field of nucleic acid therapeutics, providing critical support for mRNA therapies through mechanisms such as protecting nucleic acids and enhancing cellular uptake. Traditional LNPs consist of four components: ionizable lipids, PEGylated lipids, cholesterol, and auxiliary lipids (phospholipids). For a long time, researchers have regarded phospholipids as structural auxiliary components of LNPs, responsible for mediating LNP self-assembly and maintaining membrane stability. However, a recent study published in Biomaterials, a top-tier journal in the biomaterials field [1], has found that phospholipids play a crucial role in the membrane fusion, in vivo escape, and transfection efficiency of selectively targeted lipid nanoparticles (SORT LNPs). This research demonstrates that the functional role of phospholipids in LNPs has gone beyond their traditional positioning as “auxiliary lipi
