Third, the role of p53 mutations (the most frequent mutations in human cancers) in ferroptosis is largely overlooked; current studies have focused primarily on wild-type p53, while the impact of hotspot p53 mutations (e.g., R175H and R273H) on ferroptosis susceptibility, and whether mutant p53 retains or rewires the dual regulatory function, is unknown. The gene discussed is TP53; the disease is cancer.