Pigment epithelium-derived factor receptor (PEDF-R) (PNPLA2)

Pigment epithelium-derived factor (PEDF) is a multifunctional secreted glycoprotein belonging to the serpin family that serves as a potent endogenous inhibitor of angiogenesis and a critical neurotrophic factor (UniProt: P36955). The term Unspecified PEDF-interacting receptor/binding partners refers to a collection of cell-surface proteins that mediate these diverse biological effects, with the Pigment epithelium-derived factor receptor (PEDF-R), also known as Patatin-like phospholipase domain-containing protein 2 (PNPLA2) or Adipose triglyceride lipase (ATGL), being the most prominent (PMID: 16732272). Upon binding PEDF, PEDF-R exhibits phospholipase A2 activity, releasing signaling lipids that drive anti-angiogenic and neuroprotective pathways. Other significant binding partners include Plexin domain-containing proteins 1 and 2 (PLXDC1/2), which are involved in endothelial cell regulation, and Low-density lipoprotein receptor-related protein 6 (LRP6), which mediates PEDF's antagonism of the Wnt signaling pathway (PMID: 21602462, PMID: 24812421). Therapeutically, these interactions are explored for treating neovascular diseases like age-related macular degeneration and various cancers, where PEDF levels are typically diminished. However, because PEDF-R is also the primary enzyme responsible for triglyceride hydrolysis in adipose tissue, drug development must address the challenge of achieving tissue-specific effects to avoid systemic metabolic imbalances or conditions like Neutral Lipid Storage Disease (UniProt: Q96AD5). Current research often focuses on short PEDF-derived peptides that selectively activate specific receptor-mediated pathways to improve therapeutic precision (PMID: 23533154).

Other names

Patatin-like phospholipase domain-containing protein 2Adipose triglyceride lipaseATGLDesnutriniPLA2-zetaPigment epithelium-derived factor-binding proteinPLXDC1PLXDC2LRP6F1-ATP synthase beta subunitPEDF-R

PEDF binds to the PEDF-R (PNPLA2) receptor, triggering its phospholipase A2 activity to release signaling lipids, and also interacts with LRP6 to antagonize Wnt signaling and PLXDC1/2 to inhibit endothelial cell proliferation and migration.