A Nature Cell Biology study identified riboflavin (vitamin B2) metabolism as a modulator of ferroptosis resistance in cancer cells by stabilizing FSP1 and supporting antioxidant recycling. Researchers led by José Pedro Friedmann Angeli used CRISPR–Cas9 screening and biochemical assays to link riboflavin-derived cofactors to reduced lipid peroxidation and ferroptotic thresholds. The team showed that riboflavin deficiency sensitizes cancer cells to ferroptosis and that roseoflavin, a bacterial riboflavin analog, induced ferroptosis at low concentrations in cell models. Authors emphasized that pharmacologic inhibitors of the B2 pathway are not yet available and that translating metabolic targeting will require selective strategies to avoid systemic toxicity. This mechanistic discovery identifies a new metabolic vulnerability that could be exploited alongside existing ferroptosis-inducing therapies, particularly in tumors that upregulate redox defenses. The study provides molecular biomarkers (FSP1 stability and riboflavin pathways) for patient selection in future trials. Drug developers and translational researchers should evaluate drug-like inhibitors, delivery modalities and combination regimens. The paper frames riboflavin metabolism as both a biomarker and a target that could broaden ferroptosis-based therapeutic approaches.