1IMV517620317ENSG00000132386ENSG00000282307ENSMUSG00000000753P36955P97298NM_002615NM_001329903NM_001329904NM_001329905NM_011340NP_001316832NP_001316833NP_001316834NP_002606NP_035470Pigment epithelium-derived factor (PEDF) also known as serpin F1 (SERPINF1), is a multifunctional secreted protein that has anti-angiogenic, anti-tumorigenic, and neurotrophic functions.

Found in vertebrates, this 50 kDa protein is being researched as a therapeutic candidate for treatment of such conditions as choroidal neovascularization, heart disease, and cancer.

[6][7] Pigment epithelium-derived factor (PEDF) was originally discovered by Joyce Tombran-Tink and Lincoln Johnson in the late 1980s.

A neurotrophic protein around 50 kilodaltons (kDa) was identified and temporarily named RPE-54 before being officially termed pigment epithelium-derived factor.

[7] They found that PEDF was a previously uncharacterized protein and a member of the serpin (serine protease inhibitor) family.

[11] Immediately upstream of the PEDF gene lies a 200bp promoter region with putative binding sites for the transcription factors HNF4, CHOP, and USF.

[13] Near the C-terminus at residues 365-390 lies the reactive center loop (RCL) which is normally involved in serine protease inhibitor activity; however, in PEDF this region does not retain the inhibitory function.

[17] This effect is due to hypoxic conditions causing matrix metalloproteinases (MMPs) to proteolytically degrade PEDF.

[19] Secreted PEDF binds a receptor on the cell surface termed PEDF-R.[20] PEDF-R has phospholipase A2 activity which liberates fatty acids from glycerolipids.

[9] Expression of PEDF in the human retina is found at 7.4 weeks of gestation, suggesting it may play a role in retinal neuron differentiation.

Molecules that shift the balance towards PEDF and away from VEGF may prove useful tools in both choroidal neovascularization and preventing cancer metastasis formation.