The most common cause of blindness is abnormalities in vascularization - blood vessel formation or distribution. Better understanding how vascularization is regulated will help guide the development of new treatments for eye disease. In a recent study, researchers focused on a signaling pathway that regulates angiogenesis and metabolism. The transcription factor HIF-1α regulates vascular endothelial growth factor (VEGF), directing the cellular response to lack of oxygen. Unfortunately, although polypyrimidine tract-binding protein-associated splicing factor (PSF) is known to regulate HIF-1α, how HIF-1α signals are terminated remains unclear. Using mouse models of hypoxia, researchers examined how PSF affects HIF-1α-mediated cellular energy production, migration, and proliferation. They found that PSF prevented excess vascularization and corrected abnormal VEGF expression in mice with oxygen-induced retinopathy. PSF expression altered bioenergetic functions in the mitochondria during hypoxia and prevented endothelial cell changes. A closer look showed that PSF recruited the protein Hakai to PSF/HIF-1α complexes during hypoxia, inhibiting HIF-1α. Although further studies are needed, this is the first study to show the role of PSF in a HIF-1α/Hakai-based regulatory mechanism, suggesting that PSF may be an ideal treatment target for neovascularization-associated eye disease.