Although it remains unclear why a polyunsaturated lipid-like PI(4,5)P 2 coexists in nanodomains with cholesterol and SM-lipids typically associated with liquid-ordered membrane domains-this arrangement likely creates specialized nanodomains. These nanodomains may involve a complex interplay of membrane curvature and inter-leaflet lipid interactions, increasing membrane tension and thickness . This unique lipid organization could be key to facilitating processes requiring precise mechanical and biochemical membrane properties