CRISPR screens for the discovery of novel ferroptosis targets: progress and perspectives

Ferroptosis is a distinct, iron-dependent form of regulated cell death characterized by lipid peroxidation. Despite its growing significance in physiology and disease, the molecular networks that govern ferroptosis are not yet fully understood. Genome-wide CRISPR screens have broadened the regulatory landscape of ferroptosis by revealing both conserved and context-dependent mechanisms. In this review, we summarize recent advances in CRISPR-based ferroptosis screens, highlighting a transition from in vitro CRISPR screens to in vivo platforms and single-cell CRISPR screens. We also discuss the potential translation of key targets, focusing on their structural druggability and therapeutic potential. By outlining objective-driven screening strategies, this review seeks to provide options for exploring the distinct mechanisms of ferroptosis and to accelerate its translation into therapeutic opportunities for various diseases.