The role of Placenta growth factor (PlGF) in physiological angiogenesis is quiescent, preclinical and human studies have established PlGF angiogenic activity to be regulated in pathologies. PlGF elicits its cellular functions via (vascular endothelial growth factor receptor) VEGFR-1 alone, and has gained more attention for its safety profile, especially when compared to the risks involved in VEGF-derived therapies. Loss and gain studies of PlGF function highlight the contribution of PlGF in disease aggravation or alleviation; however, factors regulating PlGF expression remains elusive.