Collectively, our data indicate that LRP8 is required to prevent ferroptosis by maintaining high levels of GPX4 in MYCN‐amplified orthotopic neuroblastoma models and suggest that inhibition of the SELENOP/LRP8 axis as a novel and selective strategy to trigger ferroptosis and thereby limit tumor growth in highly aggressive and hard to treat MYCN‐amplified neuroblastoma cells (Fig 4I). This evidence concerns the gene SELENOP and neuroblastoma.