It now remains to be determined whether small-molecule L-phe mimetics require development or if L-phe itself is a safe and efficacious treatment for endothelial dysfunction.PerspectivesCOMPETENCY IN MEDICAL KNOWLEDGE: L-phe–mediated GCH1-GFRP activation leads to a rise in vascular BH4 levels and improved vascular relaxation in a rodent model of hypertension. Here, GCHFR is linked to endothelial dysfunction.