perilipinproteiner

Perilipinproteiner, commonly known as perilipins, are a family of lipid droplet–associated proteins that coat triglyceride-rich lipid droplets in many cell types and regulate lipid storage and mobilization. In humans the family comprises several members (PLIN1–PLIN5), each encoded by a separate gene and with distinct tissue distribution and regulation. The proteins contribute to the stability of lipid droplets and modulate access of lipases to stored triglycerides.

In adipocytes, PLIN1 is the dominant perilipin and acts as a gatekeeper of lipolysis. In the basal state it protects lipid stores by binding coactivators and restricting lipase access. Upon hormonal stimulation that raises cAMP (for example catecholamines), protein kinase A phosphorylates PLIN1 and hormone-sensitive lipase (HSL). Phosphorylated PLIN1 releases CGI-58 (ABHD5), which activates adipose triglyceride lipase (ATGL), and HSL is recruited to the droplet, together promoting triglyceride hydrolysis and fatty acid mobilization.

Other perilipins have broader or alternative roles. PLIN2 and PLIN3 are more widely expressed and associate with lipid droplets in many cell types, contributing to droplet stability. PLIN5 is enriched in oxidative tissues such as heart and skeletal muscle and coordinates lipolysis with mitochondrial fatty acid oxidation.

Dysregulation of perilipins has been linked to metabolic disorders including obesity, insulin resistance, non-alcoholic fatty liver disease, and certain cancers. Because perilipins regulate lipid flux, they are of interest as potential therapeutic targets to modulate lipolysis and energy balance.