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Lipid droplets (LDs), long overlooked as inert cellular storage organelles, are now recognized for their complex and rich biology as membraneless organelles integral to cell metabolism. Significant advances have revealed that LDs are crucial for cellular processes that include the storage and retrieval of lipids for metabolic energy and membrane synthesis and the detoxification of lipids by sequestering them in the organelle's core. Here, we review current key aspects of LD biology, emphasizing insights into fundamental mechanisms of their formation, the mechanisms of protein targeting, new insights into LD turnover, and how LDs integrate into cellular metabolism. Where possible, we describe how these processes are important in physiology and how alterations in LD biology can lead to metabolic disease. We highlight unresolved questions and key challenges to be addressed for further advancing our understanding of LD biology and its implications for health and disease.
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