GPX4 is the main enzyme regulating ferroptosis; however, a number of cancer cell lines (e.g., non-small cell lung cancer PC9, melanoma A375, and Kuramochi ovarian cancer JCRB cells) are resistant to GPX4 inhibitors [44,55,59,60,61], and the sensitivity to ferroptosis induced by GPX4 inactivation varies considerably between cancer cell types, which indicates that a parallel ferroptosis defense system to GPX4 may exist [59]. The gene discussed is GPX4; the disease is melanoma.