GCH1 (GTP cyclohydrolase 1) is the rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis, catalyzing the conversion of GTP to dihydroneopterin triphosphate 1. The enzyme plays a crucial role in cellular protection against ferroptosis, an iron-dependent form of cell death, through its production of the antioxidant BH4 1. GCH1 and BH4 prevent ferroptosis by causing lipid remodeling and selectively preventing depletion of phospholipids with polyunsaturated fatty acid tails 1. In vascular biology, endothelial cell-derived BH4 from GCH1 prevents aortic valve calcification by maintaining proper nitric oxide synthase function and preventing peroxynitrite formation 2. GCH1 deficiency in endothelial cells leads to increased oxidative stress and calcification processes 2. The gene is associated with dystonia, particularly dopa-responsive dystonia, likely through its role in dopamine synthesis pathways 3. In cancer biology, GCH1 expression levels determine ferroptosis susceptibility in cancer cells, with higher expression conferring resistance to this form of cell death 14. The GCH1-BH4 pathway represents a master regulator of ferroptosis resistance independent of the traditional GPX4/glutathione system 1.