The chapter discusses the organization and function of lipid rafts in cell membranes, emphasizing the role of lipids and proteins in membrane subcompartmentalization. Lipids, composed of hydrophobic and hydrophilic domains, form bilayers that are essential for cell identity and function. The hydrophobic effect and amphipathicity of lipids enable the spontaneous formation of lipid bilayers, which can assemble into different structural phases due to their amphipathic nature. Eukaryotic cells contain a diverse array of lipids, including glycerophospholipids, sphingolipids, and sterols, which contribute to the complexity and functionality of membranes. The bilayer is the fundamental structure of cell membranes, but it is not dominated by lipids alone; transmembrane proteins also play a crucial role. These proteins interact with lipids to modulate membrane properties and support various cellular processes. Sterols and sphingolipids are particularly important in regulating membrane thickness, stiffness, and protein sorting, which are critical for membrane trafficking and signaling events. Lipid rafts, dynamic nanoscale assemblies enriched in sphingolipids and sterols, are key players in membrane subcompartmentalization. They facilitate vesicular trafficking, endocytosis, and signaling by coalescing and forming larger domains that can be regulated by specific proteins and lipid interactions. The formation and stability of rafts are influenced by lipid composition, protein modifications, and the underlying cytoskeleton. Recent studies have revealed that plasma membranes can undergo phase separation, similar to simple model systems, under certain conditions. This phase separation can be induced by adjusting lipid composition and temperature, and it is tightly regulated by feedback mechanisms to maintain membrane homeostasis. The functionalization of nanoscale rafts through oligomerization of raft proteins or lipids further enhances their role in membrane trafficking and signaling. Overall, the chapter highlights the dynamic and complex nature of lipid rafts and their importance in regulating cellular functions, emphasizing the need for further research to understand the intricate mechanisms of lipid-protein interactions and membrane organization.The chapter discusses the organization and function of lipid rafts in cell membranes, emphasizing the role of lipids and proteins in membrane subcompartmentalization. Lipids, composed of hydrophobic and hydrophilic domains, form bilayers that are essential for cell identity and function. The hydrophobic effect and amphipathicity of lipids enable the spontaneous formation of lipid bilayers, which can assemble into different structural phases due to their amphipathic nature. Eukaryotic cells contain a diverse array of lipids, including glycerophospholipids, sphingolipids, and sterols, which contribute to the complexity and functionality of membranes. The bilayer is the fundamental structure of cell membranes, but it is not dominated by lipids alone; transmembrane proteins also play a crucial role. These proteins interact with lipids to modulate membrane properties and support various cellular processes. Sterols and sphingolipids are particularly important in regulating membrane thickness, stiffness, and protein sorting, which are critical for membrane trafficking and signaling events. Lipid rafts, dynamic nanoscale assemblies enriched in sphingolipids and sterols, are key players in membrane subcompartmentalization. They facilitate vesicular trafficking, endocytosis, and signaling by coalescing and forming larger domains that can be regulated by specific proteins and lipid interactions. The formation and stability of rafts are influenced by lipid composition, protein modifications, and the underlying cytoskeleton. Recent studies have revealed that plasma membranes can undergo phase separation, similar to simple model systems, under certain conditions. This phase separation can be induced by adjusting lipid composition and temperature, and it is tightly regulated by feedback mechanisms to maintain membrane homeostasis. The functionalization of nanoscale rafts through oligomerization of raft proteins or lipids further enhances their role in membrane trafficking and signaling. Overall, the chapter highlights the dynamic and complex nature of lipid rafts and their importance in regulating cellular functions, emphasizing the need for further research to understand the intricate mechanisms of lipid-protein interactions and membrane organization.