• Citronellal (CT) improves endothelial dysfunction in Type 1 diabetes mellitus (T1DM) rats by reversing GCH1 and Smurf2 protein expression in the aorta.
• Smurf2 is identified as the E3 ubiquitin ligase that interacts with GCH1 and promotes its degradation via the proteasome pathway in HUVECs.
• The Smurf2-GCH1 interaction regulates GCH1 stability, affecting BH4/eNOS signaling and endothelial function.
• Targeting the Smurf2-GCH1 axis may offer a novel therapeutic strategy for endothelial injury in cardiovascular diseases.