AUP1 (ancient ubiquitous protein 1) is a cytoplasmic lipid droplet-associated protein that regulates lipid homeostasis through multiple interconnected pathways. Primary function: AUP1 localizes to lipid droplets and regulates their organization and degradation 1. The protein undergoes monoubiquitination, which promotes lipid droplet clustering through homophilic or heterophilic interactions 1. Mechanistically: AUP1 functions as a critical lipophagy factor, working with co-factor UBE2G2 to facilitate selective autophagy-mediated degradation of lipid droplets 2. This process is essential for cholesterol efflux in macrophage foam cells and lipid homeostasis 2. During viral infections, particularly dengue, AUP1's acyltransferase activity triggers lipophagy to mobilize lipids supporting viral replication 3. Recently, AUP1-UBE2G2 complexes were found to negatively regulate STING signaling by retaining STING in the endoplasmic reticulum, thereby controlling innate immune responses 4. Disease relevance: AUP1 dysfunction contributes to fatty liver diseases, atherosclerosis risk, and viral susceptibility 5. Clinical significance: AUP1 represents a therapeutic target for enhancing lipophagy to treat atherosclerosis and metabolic diseases, while its regulation of STING provides implications for antiviral immunity and autoinflammatory conditions 24.