Peroxiredoxins in the kidney: a Jekyll and Hyde existence in disease pathogenesis.

Oxidative stress is a well-established driver in the pathogenesis and progression of various kidney diseases. The peroxiredoxin (PRDXs) family, comprising typical 2-Cys, atypical 2-Cys, and 1-Cys members, serves as essential thiol-dependent peroxidases that maintain cellular redox balance. Unlike classical antioxidant enzymes that solely scavenge reactive oxygen species, PRDXs are unique in their ability to undergo redox-sensitive structural transitions, functioning as molecular chaperones and intracellular signaling hubs. In the kidney, PRDXs exert multifaceted protective roles by preserving mitochondrial integrity and attenuating inflammatory and fibrotic signaling. Interestingly, beyond these canonical functions, several PRDX members exhibit context-dependent detrimental effects that paradoxically aggravate renal injury. Such dual functionality is regulated through sophisticated mechanisms, including specific post-translational modifications, molecular chaperone switching, and extracellular release as damage-associated molecular patterns. Although PRDXs represent promising therapeutic targets and biomarkers, their functional duality poses considerable challenges for drug development. Future efforts must focus on spatiotemporally precise regulation to selectively augment PRDXs-mediated defense while mitigating their injury-promoting effects.