By interfering with COX4I2 mRNA in fibroblasts, we observed a decrease in the expression of ANG1 and HGF, which suggests that COX4I2 may act as an upstream gene of ANG1 and HGF to mediate a pathway of pheochromocytoma angiogenesis. Here, COX4I2 is linked to hereditary pheochromocytoma-paraganglioma.