Using in vitro (Oxygen-Glucose Deprivation/Reperfusion (OGD/R)-treated Pheochromocytoma Cell Line 12 (PC12) cells ) and in vivo (rat spinal cord ischemia-reperfusion (I/R) ) models, we demonstrate that GPR68 downregulation exacerbates ferroptosis, evidenced by elevated Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4), Malondialdehyde (MDA), and Oxidized Glutathione/ Total Glutathione (GSSG/T-GSH) levels, alongside reduced Solute Carrier Family 7 Member 11 (SLC7A11) and Glutathione Peroxidase 4 (GPX4). Here, ACSL4 is linked to pheochromocytoma.