Lipid droplets are essential organelles involved in lipid and energy homeostasis, consisting of a hydrophobic core of neutral lipids enclosed by a phospholipid monolayer. They are highly dynamic and interact with various cellular organelles, including the endoplasmic reticulum (ER), peroxisomes, mitochondria, and lysosomes. These interactions are crucial for lipid droplet biogenesis, degradation, and cellular metabolism. Lipid droplets facilitate the coordination between different organelles and act as hubs in cellular metabolism. The biogenesis of lipid droplets involves multiple steps, starting with the synthesis of neutral lipids such as triacylglycerols and sterol esters in the ER. These lipids coalesce to form an oil lens, which then buds from the ER membrane through a process influenced by membrane curvature and surface tension. Key proteins like FIT1 and FIT2 promote lipid droplet budding, while seipin stabilizes the ER-lipid droplet interface and facilitates lipid droplet growth and maturation. Proteins targeting lipid droplets can be categorized into two classes: those that stably associate with membranes (Class I) and those recruited directly from the cytosol (Class II). Class I proteins often have hydrophobic hairpins that insert into lipid bilayers, while Class II proteins bind through amphipathic α-helices, which interact with phospholipid packing defects. Lipid droplets form membrane contact sites with other organelles, such as the ER, nuclear envelope, mitochondria, peroxisomes, and lysosomes. These contacts facilitate lipid exchange, metabolite transport, and regulation of organelle division and trafficking. For example, lipid droplet-mitochondria contacts are important for fatty acid β-oxidation and ATP synthesis, while lipid droplet-lysosome contacts are involved in the degradation of perilipin family members via chaperone-mediated autophagy (CMA). Lipid droplets also play a protective role against lipotoxicity by sequestering fatty acids, preventing their toxic effects on cellular membranes. They are critical in maintaining ER homeostasis and initiating the unfolded protein response (UPR) to address ER stress. Overall, lipid droplets are vital for lipid and energy homeostasis, serving as hubs for cellular communication and regulation.Lipid droplets are essential organelles involved in lipid and energy homeostasis, consisting of a hydrophobic core of neutral lipids enclosed by a phospholipid monolayer. They are highly dynamic and interact with various cellular organelles, including the endoplasmic reticulum (ER), peroxisomes, mitochondria, and lysosomes. These interactions are crucial for lipid droplet biogenesis, degradation, and cellular metabolism. Lipid droplets facilitate the coordination between different organelles and act as hubs in cellular metabolism. The biogenesis of lipid droplets involves multiple steps, starting with the synthesis of neutral lipids such as triacylglycerols and sterol esters in the ER. These lipids coalesce to form an oil lens, which then buds from the ER membrane through a process influenced by membrane curvature and surface tension. Key proteins like FIT1 and FIT2 promote lipid droplet budding, while seipin stabilizes the ER-lipid droplet interface and facilitates lipid droplet growth and maturation. Proteins targeting lipid droplets can be categorized into two classes: those that stably associate with membranes (Class I) and those recruited directly from the cytosol (Class II). Class I proteins often have hydrophobic hairpins that insert into lipid bilayers, while Class II proteins bind through amphipathic α-helices, which interact with phospholipid packing defects. Lipid droplets form membrane contact sites with other organelles, such as the ER, nuclear envelope, mitochondria, peroxisomes, and lysosomes. These contacts facilitate lipid exchange, metabolite transport, and regulation of organelle division and trafficking. For example, lipid droplet-mitochondria contacts are important for fatty acid β-oxidation and ATP synthesis, while lipid droplet-lysosome contacts are involved in the degradation of perilipin family members via chaperone-mediated autophagy (CMA). Lipid droplets also play a protective role against lipotoxicity by sequestering fatty acids, preventing their toxic effects on cellular membranes. They are critical in maintaining ER homeostasis and initiating the unfolded protein response (UPR) to address ER stress. Overall, lipid droplets are vital for lipid and energy homeostasis, serving as hubs for cellular communication and regulation.