The Role of Ubiquitination and Deubiquitination in the Pathogenesis of Acute Kidney Injury: Progress in Research

Acute kidney injury (AKI) remains a critical clinical challenge due to its complex pathophysiology and lack of targeted therapies. We hypothesize that the ubiquitin-proteasome system (UPS) and ubiquitin-like modifiers (UBLs) are not merely isolated players but constitute an intricate and coordinated regulatory network whose dysregulation is a central driving force in AKI progression. This review synthesizes the pivotal roles of the ubiquitin–proteasome system and ubiquitin-like modifiers in driving AKI progression, emphasizing their regulation of inflammatory responses, cell death pathways (apoptosis, pyroptosis, ferroptosis), mitochondrial dysfunction, and aberrant repair. We detail enzymatic cascades involving E1-E2-E3 ligases, deubiquitinating enzymes, and ubiquitin-like modifiers (SUMOylation, neddylation, ISGylation, UFMylation), highlighting their integration into a coordinated network modulating NF-κB/NLRP3 signaling, mitophagy, and growth factor pathways, thereby providing novel strategies for targeted therapy.