Research advances of disulfidptosis in inflammatory diseases

Disulfidptosis represents a distinct regulated cell death (RCD) characterized by its induction through disulfide stress. Its core mechanism involves cysteine metabolic imbalance and nicotinamide adenine dinucleotide phosphate (NADPH) depletion, leading to actin cytoskeletal collapse. While current research primarily focuses on its role in tumors, its implications in inflammatory diseases remain elusive. This review systematically delineates the molecular mechanisms of disulfidptosis, distinguishes it from classical RCD modalities such as apoptosis, pyroptosis, and ferroptosis, and elucidates its pathophysiological contributions to inflammatory disorders. We further summarize its involvement in specific inflammatory conditions, including sepsis, osteoarthritis, and ulcerative colitis, alongside therapeutic strategies targeting solute carrier family 7-member 11 (SLC7A11)-mediated metabolic regulation, inhibition of the Rac pathway, and cytoskeletal stabilization. Current controversies persist regarding its independence as a distinct RCD entity and its crosstalk mechanisms with ferroptosis and pyroptosis. Future investigations should prioritize deciphering the molecular regulatory network of disulfidptosis, clarifying organ-specific mechanisms, and advancing clinical translation to identify novel therapeutic targets for the precision management of inflammatory diseases.