These findings partially support the notion that Drp1 aggravates hypercalcemia-induced neuronal injury following CKD by triggering mitochondrial fragmentation via activation of ROS/HIF-1α/EZH2 axis, yet whether GSK-126 and other EZH2 inhibitors have neuroprotective effects on CKD requires additional investigation. Here, EZH2 is linked to hypercalcemia disease.