The asymmetric distribution of these lipid types in the plasma membrane likely plays a role in mediating FGF2 membrane translocation. Cholesterol and SM enrichment in the outer leaflet and PI(4,5)P 2 primarily located in the inner leaflet highlights a spatial organization that supports membrane-associated processes. This asymmetry may create functional lipid environments, such as ordered nanodomains, that facilitate the recruitment and translocation of FGF2 during unconventional secretion. Thus, developing methods to reproduce this lipid asymmetry in vitro reconstitution experiments or to disrupt it in living cell systems selectively could provide insights into how these lipid distributions regulate FGF2 secretion. Such studies will uncover mechanistic details about the secretory mechanism of FGF2 and reveal broader principles about the interplay between lipid organization and protein function in cellular membranes.