PANoptosis: an emerging programmed cell death pathway in neurological diseases mechanisms and therapeutic translation.

PANoptosis is an emerging programmed cell death (PCD) pathway that integrates the key features of pyroptosis, apoptosis, and necroptosis, and is coordinately regulated by a multi-protein complex known as the PANoptosome. This pathway plays a significant role in various neurological disorders, including cerebral ischemia-reperfusion injury, spinal cord injury, glioma, and other neuroinflammatory diseases. By synthesizing the latest bioinformatics and substantial experimental evidence, this review provides a comprehensive overview of the PANoptosome's composition and its dynamic regulatory networks, and further dissect the immunoregulatory functions of PANoptosis. Distinct from previous descriptive summaries, we propose a refined framework focusing on the spatiotemporal and cell-type-specific dynamics of PANoptosis, specifically highlighting the functional transition from acute neuronal stress (VDAC1-mediated) to chronic glial-mediated inflammation (TAK1-dependent). Furthermore, we evaluate the methodological standards for detection and discuss the translational feasibility and safety of targeting this pathway. By outlining these prospective research avenues, this work underscores the critical value of PANoptosis in clinical translation and provides an updated conceptual roadmap for future therapeutic strategies in neurological diseases.