Functional rescue experiments showed that CISD2 overexpression in Smad3-knockdown mesenchymal-like bladder cancer cells reversed abnormal increases in Fe2+, ROS, LPO, and MDA while restoring GSH levels, indicating that Smad3 modulates ferroptosis through a CISD2-dependent pathway. The gene discussed is SMAD3; the disease is urinary bladder carcinoma.