{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPerilipin 5 (PLIN5) is a lipid droplet–associated protein predominantly expressed in oxidative tissues that plays a key role in regulating lipolysis. PLIN5 interacts directly with adipose triglyceride lipase (ATGL) and its co‐activator CGI-58 to modulate the release of fatty acids: under basal conditions, it restrains lipolysis to prevent excessive fatty acid release and lipotoxicity, whereas upon metabolic stress and PKA-mediated phosphorylation, it shifts toward promoting lipolysis and directing fatty acids toward mitochondrial oxidation for energy production. This bidirectional regulatory capacity is fundamental for maintaining cellular energy homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn skeletal muscle, PLIN5 abundance is dynamically regulated by physiological stimuli such as endurance and high-intensity training, where its upregulation is closely linked to increased intramyocellular lipid (IMTG) turnover and improved insulin sensitivity. Notably, PLIN5 localizes not only to the surface of lipid droplets but also to mitochondria, thereby establishing contact sites that facilitate the direct transfer of fatty acids for oxidation. This anatomical and functional coupling contributes to enhanced metabolic flexibility and oxidative capacity, underpinning the athlete’s paradox in which high lipid content coexists with efficient fuel utilization."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond skeletal muscle, PLIN5 plays an instrumental role in regulating lipid droplet accumulation and fatty acid metabolism in other highly oxidative tissues such as the liver and heart. In these organs, alterations in PLIN5 expression are associated with metabolic disturbances—including hepatic steatosis, cardiomyopathies, and insulin resistance—and experimental models have demonstrated that enhanced PLIN5 expression can protect cells by reducing oxidative stress and apoptosis. Furthermore, emerging evidence suggests that circulating PLIN5 may serve as a novel biomarker for myocardial infarction, highlighting its relevance not only for intracellular lipid management but also for systemic metabolic health."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hong Wang, Ming Bell, Urmila Sreenivasan, et al. 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