PLIN2 (perilipin 2) is a structural component of lipid droplets that plays essential roles in lipid metabolism and cellular energy homeostasis. PLIN2 is required for the formation and maintenance of lipid storage droplets, serving as a stabilizing protein on the lipid droplet surface 1. The protein undergoes dynamic regulation through post-translational modifications, including phosphorylation by PFKL under glucose starvation conditions, which promotes its interaction with CPT1A to facilitate lipid droplet-mitochondria tethering for enhanced fatty acid oxidation 2. PLIN2 is subject to ubiquitin-mediated degradation, with essential amino acids like leucine and isoleucine promoting its polyubiquitination and subsequent degradation to ameliorate hepatic steatosis 1. In disease contexts, PLIN2 accumulates in degenerating microglia associated with white matter injury and ferroptosis 3, and is upregulated in alcoholic liver disease through Setdb1 suppression, contributing to hepatosteatosis 4. PLIN2 also promotes colorectal cancer progression through CD36-mediated epithelial-mesenchymal transition 5. Additionally, PLIN2-containing lipid droplets in microglia facilitate cholesterol transfer to neuronal progenitor cells, supporting brain development 6. These findings highlight PLIN2's central role in lipid homeostasis and its involvement in various pathological conditions.