Structural biology studies employing cryo-electron microscopy and biochemical reconstitution have revealed how the membrane protein TTYH2 interacts with disc-shaped APOE-containing lipoprotein particles to facilitate lipid transfer within endosomes. Findings showed the formation of multiple oval-shaped assemblies consistent with authentic APOE-laden nanoparticles incorporating cholesterol and phospholipids. This molecular insight advances understanding of membrane lipid homeostasis and provides a foundation for exploring cellular lipid transport pathways affecting health and disease.