Perilipin-1 (PLIN1) (PLIN1)

Perilipin-1 (PLIN1) is a major protein that coats lipid droplets in adipocytes, the primary fat-storing cells in adipose tissue. It is a member of the perilipin (PAT) family and is encoded by the PLIN gene. The name "Perilipin-1" (PLIN1) is the most widely accepted and scientifically precise designation. Alternative names such as "Perilipin" or "PLIN" are less specific, as they may refer to the broader family rather than this specific isoform. The UniProt symbol is "PLIN1", and the gene symbol is also "PLIN". "FPLD4" refers to Familial Partial Lipodystrophy type 4, a disorder associated with PLIN1 mutations. The PAT domain is a conserved structural feature of the perilipin family. Under basal conditions, PLIN1 forms a protective barrier around lipid droplets, shielding stored triglycerides from hydrolysis by cytosolic lipases such as hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). In response to hormonal signals (e.g., catecholamines acting via β-adrenergic receptors), PLIN1 is phosphorylated by protein kinase A (PKA), altering its conformation and enabling the recruitment of lipases to the lipid droplet surface, thus facilitating lipolysis and the release of fatty acids for energy metabolism. PLIN1 also plays a role in the formation and enlargement of lipid droplets by regulating triacylglycerol synthesis and turnover. Its activity is dynamically modulated by specific lipid interactions and segregation into distinct microdomains on the lipid droplet surface. Genetic variations and mutations in PLIN1 are associated with altered fat storage, obesity susceptibility, and metabolic disorders, underscoring its central role in lipid metabolism and energy homeostasis. PLIN1 is classified as a lipid droplet-associated structural protein and is a founding member of the PAT (perilipin, adipophilin, TIP47) family, now expanded to include perilipins 1 through 5. It is not an enzyme, receptor, or transporter, but rather a scaffold protein that modulates enzyme access to lipid substrates. PLIN1 is implicated in obesity, insulin resistance, type 2 diabetes, lipodystrophy, and related metabolic disorders. Both elevated and reduced PLIN1 expression are associated with metabolic dysfunction, highlighting its role as a crucial regulator of adipose tissue homeostasis. PLIN1 is recognized as a potential therapeutic target for metabolic diseases due to its central role in lipid storage and mobilization, but there are currently no approved drugs specifically targeting PLIN1.

Other names

Perilipin-1PLIN1PERIPLINLipid droplet-associated proteinFPLD4PerilipinPerilipin APerilipin BPerilipin CPAT family domain-containing lipid droplet protein 1