perilipin

Perilipin is a family of lipid droplet-associated proteins that regulate lipid storage and mobilization in cells. In mammals, the perilipin family comprises PLIN1 through PLIN5, each containing a PAT domain and localizing primarily to cytosolic lipid droplets involved in triglyceride storage.

Perilipins coat the surface of lipid droplets in adipocytes and many other cell types. They control access of lipases to triglycerides and thereby govern the rate of lipolysis. In adipocytes, perilipin-1 (PLIN1) is abundant; in nonadipose tissues PLIN2 (ADRP) and PLIN3 (TIP47) are common; PLIN5 is enriched in oxidative tissues such as heart and skeletal muscle.

Regulation of lipolysis occurs largely via phosphorylation by protein kinase A (PKA) in response to catecholamines. When perilipin is non-phosphorylated, it helps sequester lipases and the lipolytic coactivator CGI-58, limiting triglyceride breakdown. Phosphorylation of perilipin, and of hormone-sensitive lipase (HSL), promotes lipase access to lipid droplets and release of fatty acids and glycerol. CGI-58 (ABHD5) is released from perilipin upon phosphorylation, activating adipose triglyceride lipase (ATGL) and accelerating triglyceride hydrolysis.

Clinically, altered perilipin expression or mutations can affect lipid storage and energy metabolism and have been implicated in metabolic disorders such as obesity and insulin resistance, though the precise contributions vary by isoform and tissue.