Nature Metabolism, Published online: 23 March 2026; doi:10.1038/s42255-026-01483-2By determining the organellar topology and proteome of fat-oxidizing and fat-synthesizing hepatocytes, Kang et al. show that perilipin 5-mediated mitochondria–lipid droplet contacts facilitate the expansion of lipid droplets in both populations and are impaired in early metabolic dysfunction-associated steatotic liver disease (MASLD).
