PLIN5 (perilipin 5) is a lipid droplet-associated protein that regulates fatty acid metabolism in oxidative tissues including skeletal muscle, liver, and heart 1. PLIN5 functions as a scaffolding protein that maintains the balance between lipid storage and mobilization 2. Under basal conditions, PLIN5 inhibits lipolysis by sequestering CGI-58 and reducing adipose triglyceride lipase (ATGL) activity 2. Upon PKA-mediated phosphorylation during energy stress, PLIN5 releases these inhibitory interactions, promoting lipolysis and fatty acid mobilization 2. PLIN5 also tethers mitochondria to lipid droplets through interactions with mitochondrial proteins including Rab8a and FATP4, facilitating direct transfer of fatty acids to mitochondria for β-oxidation 34. This LD-mitochondria contact is dynamically regulated by AMPK and stress signals including fasting and exercise 4. In disease contexts, PLIN5 dysregulation contributes to metabolic dysfunction. Enhanced PLIN5 expression protects against fatty liver disease and alcohol-induced liver injury by promoting mitochondrial function and preventing lipid accumulation 56. Conversely, impaired PLIN5 function is implicated in diabetic cardiomyopathy through lipid toxicity and mitochondrial dysfunction 7.