Optimizing LNPs presents a multi-variable challenge. Typically, the composition of LNPs consists of a base mixture comprising an ionizable lipid, a sterol, a helper lipid like DSPC or PE, and a PEGylated lipid. Several studies have focused on optimizing the ionizable lipid, with the emphasis on apparent pKa, fusion efficacy and biodegradability . Other studies have investigated the role of the helper lipid in LNP structure and fusion . Recent studies are now beginning to reveal the impact of replacing commonly used cholesterol with alternative sterols, such as plant sterol 𝛽 -sitosterol. These investigations demonstrate that such substitutions not only alter LNP properties like shape and structure but can also markedly improve fusion efficacy .