Targeting panoptosis: a narrative review of its therapeutic potential in kidney disease.

Abstract

Renal diseases are major global public health challenges due to their complex mechanisms and growing burden. PANoptosis, a unified programmed cell death pathway driven by the PANoptosome complex, involves the combined activation of pyroptotic, apoptotic, and necroptotic signaling, significantly contributing to renal tissue damage. This review systematically explores PANoptosis's composition, regulatory mechanisms, and its role in kidney pathologies such as AKI, CKD, DKD, and renal tumors. It also examines the interplay between PANoptosis and key cellular processes like mitochondrial dysfunction, ER stress, non - coding RNAs, ferroptosis, and autophagy. Preclinical studies suggest that targeting PANoptosis - related molecules (e.g., Z-DNA Binding Protein 1(ZBP1), caspase - 8, NOD-like receptor thermal protein domain associated protein 3(NLRP3)) shows therapeutic potential for kidney diseases. However, clinical application is currently limited due to insufficient human data. Future research should focus on validating PANoptosis biomarkers in renal diseases, developing cell - death - context - specific inhibitors and agonists, and clarifying its advantages over single - mode cell death modulation. This review highlights PANoptosis as a promising therapeutic strategy while addressing unresolved issues in nephrology research.