Placenta growth factor (PLGF) was initially cloned form a term placenta cDNA library. PLGF is a dimeric glycoprotein with 53% homology to VEGF. As a result of alternative splicing, four isoforms for PLGF has been described, PLGF-1, PLGF-2, PLGF-3, and PLGF-4.? PLGF-2 binds to heparin with high affinity, whereas neither PLGF-1, PLGF-3, nor PLGF-4 bind heparin. PLGF-2 is the only isoform in mouse. PLGF binds to VEGFRI but not to VEGFRII; also PLGF binds to sVEGF1. PLGF plays a key role in the maternal vascular function during pregnancy. Low levels of PLGF have been associated with patients experiencing preeclampsia and delivering small-for-gestational age (SGA) neonates. High expression of PLGF has been associated to colorectal cancer (CRC), and its expression in CRC tissues correlates with high levels of MMP-9 and VEGF1. PLGF has been shown to increase tumor cell migration in lung cancer, leukemia, and melanoma cells. In colorectal cancer, PLGF induces tumor cell migration and invasion through upregulation of MMP9. ?PLGF is expressed in the majority of medulloblastomas, and high expression of PLGF receptor neuropilin 1 (Nrp1) correlates with poor survival in patients. In a mouse model, PLGF/Nrp1 blockade provided direct antitumor effects in vivo, medulloblastoma regression, decreased metastasis, and increased survival.