Disulfidptosis: Mechanisms, evidence boundaries, and translational opportunities

Disulfidptosis has rapidly emerged as a regulated cell death mechanism linked to cystine stress, aberrant disulfide accumulation, and collapse of the actin cytoskeleton, particularly in contexts shaped by high SLC7A11 activity and impaired NADPH-dependent reducing capacity. However, the literature has expanded faster than the mechanistic standards used to classify this process, and studies invoking disulfidptosis now range from direct experimental demonstrations to purely association-based bioinformatic analyses. This heterogeneity creates a growing risk of overassignment of the term and blurs the boundary between bona fide disulfidptosis and related redox or metabolic stress phenotypes. In this review, we prioritize studies that provide direct mechanistic support for disulfidptosis and propose a practical evidence-tier framework for mechanistic assignment. Rather than treating all "disulfidptosis-related" reports as equivalent, we distinguish high-confidence evidence from inferential or hypothesis-generating observations and discuss the interpretive limitations of lower-tier claims. We synthesize current knowledge on the biochemical basis, cellular prerequisites, morphological and molecular hallmarks, experimental readouts, and disease contexts of disulfidptosis. By emphasizing rigorous evidence interpretation and integrating multi-omics prediction, mechanistic crosstalk, and clinically tractable therapeutic strategies, this review outlines the current conceptual boundaries of disulfidptosis and offers a useful reference for future mechanistic research and translational development.