Editorial: Ferroptosis, cuproptosis, and triaptosis: unveiling pathways and translational prospects

Programmed cell death (PCD) is a fundamental feature of multicellular life, governing development, tissue homeostasis, ageing, and disease progression (Newton et al., 2024).While apoptosis, necroptosis, and pyroptosis have long dominated the conceptual framework of PCDs, the past decade has witnessed the rapid emergence of noncanonical modalities shaped by metal-and element-associated metabolic and redox perturbations. Among these, ferroptosis and cuproptosis have established themselves as mechanistically distinct and biologically consequential pathways, while triaptosis has recently been proposed as an oxidative stress-linked form of PCD associated with endosomal dysfunction (Dixon et al., 2012;Tsvetkov et al., 2022;Swamynathan et al., 2024). Mechanistically, ferroptosis is driven by iron-dependent lipid peroxidation and cuproptosis by copper-triggered mitochondrial proteotoxicity, whereas triaptosis is distinctively characterized by PI(3)P-dependent endosomal stress. Together, these modalities highlight a growing appreciation that metal ion homeostasis and redox balance are not merely modifiers of cell metabolism, but central determinants of Together, these studies underscore the emerging relevance of cuproptosis in diseases, linking copper-dependent cell death to cardiovascular pathology and diagnostic potential.Triaptosis is introduced in this Research Topic as a proposed oxidative stress-driven form of regulated cell death linked to endosomal dysfunction (Swamynathan et al., 2024). Although its molecular framework is less established than that of ferroptosis or cuproptosis, its inclusion highlights an important conceptual advance: dysregulated redox signaling can engage PI(3)P-dependent endosomal pathways to actively shape cell death outcomes. The discussion of triaptosis in this collection is intentionally exploratory, aimed at stimulating rigorous mechanistic and genetic investigation. As with ferroptosis in its early stages, future progress in triaptosis research will depend on the identification of defining molecular markers, core regulators, and physiological or pathological contexts in which this process operates (Qiao et al., 2025).Several overarching themes emerge from this Research Topic, highlighting key priorities for future research. First, mechanistic precision remains essential. For ferroptosis and cuproptosis, efforts should distinguish core execution machinery from context-dependent modulators, while for triaptosis, first-in-class chemical inhibitors and deeper molecular insights are needed. Second, cross-talk between death pathways warrants further exploration, as ferroptosis, cuproptosis, and oxidative stress-associated programs may intersect or compete depending on metabolic state, metal availability, and cellular context, especially in diseases with metabolic dysregulation and chronic inflammation. Third, translational integration remains a central challenge. Although ferroptosis modulators approach clinical relevance, reliable biomarkers, patient stratification, and delivery strategies remain limiting factors. Comparable translational frameworks should be developed early for cuproptosis-and triaptosis-targeted interventions to avoid repeating prior bottlenecks. Finally, metallo-redox biology emerges as a unifying concept: iron and copper are not merely toxic catalysts but integral components of cellular signaling networks. Future studies leveraging metallomics, spatial imaging, and systems-level approaches will be essential to decode how metal ions orchestrate cell fate in health and disease.The articles collected in this Research Topic reflect both consolidation and expansion within the field of PCD. By integrating established knowledge of ferroptosis with emerging insights into cuproptosis and triaptosis, this collection highlights the evolving complexity of cell death biology and its translational promise. We thank all authors and reviewers for their valuable contributions and hope that this Research Topic will stimulate continued innovation at the intersection of PCDs, metal/ion homeostasis, and redox biology.