Perilipin-3 (PLIN3)

Perilipin-3 (PLIN3) is a soluble cytosolic protein of the perilipin family that specifically localizes to the surface of intracellular lipid droplets (LDs), playing a key role in the biogenesis, stabilization, and metabolism of LDs[1][2][3]. Structurally, PLIN3 contains three domains: an N-terminal PAT domain (unique to perilipins), a central amphipathic helical repeat region, and a C-terminal four-helix bundle[1][2]. PLIN3, through its PAT domain, binds diacylglycerol (DAG) and is recruited to membrane locations enriched in lipogenic precursors (DAG and phosphatidic acid); this membrane association facilitates the nucleation and stabilization of nascent LDs at specific ER subdomains[1][2][3]. PLIN3 is not a receptor, enzyme, or canonical drug target, but rather acts as a membrane organizer and scaffold protein to coordinate neutral lipid clustering and LD protein recruitment, with crucial roles in early LD biogenesis and lipid compartmentalization[1][2][3]. PLIN3 has been referred to by several alternative names including TIP47 (tail-interacting protein of 47 kDa) and M6PRBP1 (mannose-6-phosphate receptor-binding protein 1), reflecting its historical identification in different biological contexts, such as in endosomal transport or placental protein studies. However, its central and best established role is as a cytoplasmic scaffold protein at the lipid droplet interface[1][2][3]. While not a direct therapeutic target, it is implicated in cellular lipid homeostasis, and altered expression or localization has been linked to certain pathologic conditions, including cancer and metabolic disease[2]. No approved drugs selectively target perilipin-3, and it is not currently used as a clinical biomarker. There are no known specific safety concerns or therapeutic challenges associated with modulating PLIN3, since selective pharmacological agents do not exist and the protein’s role is largely structural/metabolic in normal cells[2].

Other names

Perilipin-3PLIN3M6PRBP1TIP4747 kDa MPR-binding proteinPP17Cargo selection protein TIP47Mannose-6-phosphate receptor-binding protein 1Placental protein 17MPR-binding proteinTail-interacting protein 47 kDaTesticular tissue protein Li 114