PLIN5

Perilipin 5 (PLIN5), also known as OXPAT or MLDP, is a member of the perilipin family of lipid droplet–associated proteins. In humans, the PLIN5 gene encodes the protein that localizes primarily to the surface of lipid droplets in oxidative tissues. PLIN5 is abundantly expressed in heart and skeletal muscle and is also present in liver and brown adipose tissue.

Functionally, PLIN5 regulates lipid storage and mobilization by controlling access of lipases to triacylglycerols within lipid droplets. It interacts with adipose triglyceride lipase (ATGL) and its coactivator CGI-58, modulating basal and stimulated lipolysis. In many oxidative tissues, PLIN5 also associates with mitochondria and appears to coordinate lipolysis with mitochondrial fatty acid oxidation, effectively channeling released fatty acids for beta-oxidation.

Regulation of PLIN5 activity occurs through phosphorylation, notably by protein kinase A in response to adrenergic signals, which can alter lipase access and lipolysis rates. AMPK signaling and nutritional status can influence PLIN5 expression and function, integrating cellular energy state with lipid handling.

Physiologically, PLIN5 supports sustained fatty acid utilization in tissues with high energy demands by linking lipid droplets to mitochondria and regulating oxidation. Altered PLIN5 expression or function has been observed in metabolic disorders such as obesity, insulin resistance, and fatty liver disease, where impaired lipid handling and oxidation are common features. Ongoing research aims to clarify tissue-specific roles and the precise molecular interactions between PLIN5, lipases, and mitochondria.