Patatin-like phospholipase domain-containing protein 2 (PNPLA2) (PNPLA2)

Patatin-like phospholipase domain-containing protein 2 (PNPLA2), commonly referred to as the Pigment Epithelium-Derived Factor Receptor (PEDF-R), is a key transmembrane protein expressed on various ocular tissues, including limbal stem cells (Notari et al., 2006, J Biol Chem). It serves as the primary mediator for the biological actions of Pigment Epithelium-Derived Factor (PEDF), a potent neurotrophic and anti-angiogenic glycoprotein (Subramanian et al., 2013, Prog Retin Eye Res). Upon binding PEDF, the receptor's intrinsic phospholipase A2 activity is activated, leading to the release of signaling molecules that promote the self-renewal and survival of limbal stem cells while inhibiting apoptosis (Ho et al., 2015, Stem Cells). This interaction is vital for maintaining the corneal epithelial barrier and the transparency of the cornea by preventing neovascularization (He et al., 2015, Invest Ophthalmol Vis Sci). In the context of disease, a deficiency in PEDF or its receptor signaling is associated with limbal stem cell deficiency and pathological blood vessel growth in the eye. Therapeutic strategies targeting PEDF-R primarily involve the use of PEDF-mimetic peptides designed to stimulate the receptor's regenerative and protective pathways. However, because PNPLA2 is also the rate-limiting enzyme in systemic triglyceride hydrolysis (as ATGL), drug development must account for potential metabolic side effects (Zimmermann et al., 2004, Science).

Other names

Pigment epithelium-derived factor receptorPEDF-RAdipose triglyceride lipaseATGLDesnutrinCalcium-independent phospholipase A2 zetaiPLA2-zetaTTS-2.2

Agonism of the PEDF receptor to trigger phospholipase A2 activity and downstream pro-survival signaling pathways like MAPK/ERK.