Key questions in ferroptosis

Ferroptosis, defined as iron-catalyzed necrotic cell death, has attracted tremendous attention over the past decade, resulting in tens of thousands of peer-reviewed publications.This surge of interest is primarily driven by two concepts: (i) the potential to eliminate cancer cells through ferroptosis, and (ii) the hypothesis that inhibiting ferroptosis could prevent tissue damage in a range of common disorders, including stroke, myocardial infarction, acute kidney, liver, and lung injuries, intoxications, adverse drug effects, as well as clinical scenarios such as solid organ transplantation.In my view, this enthusiasm has created a "gold rush" among researchers, which has, at least partially, overshadowed some fundamental questions that have remained unresolved since ferroptosis was first described.In a deliberately subjective manner, I reflect on some of these questions, aiming both to remind early-career researchers of these blind spots on the path to clinical translation and to encourage established investigators to continue the scientific debate.