perilipiin

Perilipin is a family of lipid droplet–associated proteins that coat the surface of cytoplasmic lipid droplets in many cell types. The best-known member is perilipin-1 (PLIN1), predominantly expressed in adipocytes, where it plays a central role in regulating fat storage and mobilization. Other members include perilipin-2 (PLIN2, also called adipophilin), perilipin-3 (PLIN3, TIP47), perilipin-4 (PLIN4, S3-12), and perilipin-5 (PLIN5, also known as MLDP or OXPAT). These proteins share conserved motifs that target them to lipid droplets, notably a PAT domain that mediates droplet association.

Perilipins localize to the surface of lipid droplets and modulate access of lipases to stored triglycerides. In basal conditions, perilipin-1 helps restrain lipolysis by limiting lipase activity. In response to hormonal signals, protein kinase A–mediated phosphorylation of perilipin-1 promotes conformational changes and recruitment or activation of lipases such as hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), often via the coactivator CGI-58, thereby enhancing lipolysis. Perilipin-5 is enriched in tissues with high oxidative capacity and is linked to coordination of lipolysis with mitochondrial fatty acid oxidation. Other perilipins contribute to lipid droplet stability and turnover and may have tissue-specific roles.

Tissue distribution varies among family members: PLIN1 is abundant in adipose tissue, PLIN2 and PLIN3 are more ubiquitously expressed, and PLIN5 is prominent in heart and skeletal muscle and brown adipose tissue. Altered perilipin expression or function has been associated with metabolic regulation and disease in humans and animal models.

See also: lipid droplet, lipolysis, HSL, ATGL, CGI-58 (ABHD5).