E3 ligases in acute kidney injury: Mechanistic insights and therapeutic potential

Acute kidney injury is a life‑threatening clinical syndrome that poses a major therapeutic challenge. Protein ubiquitination, a key post‑translational modification, has emerged as a critical regulator of acute kidney injury pathogenesis. E3 ubiquitin ligases, the substrate‑recognition components of the ubiquitin system, determine the fate and function of target proteins via diverse ubiquitin chain topologies. Despite increasing interest, the mechanistic roles of specific E3 ligases in AKI remain incompletely defined. Here, we categorize and summarize the functions of key AKI‑relevant E3 ligases based on four pathophysiological processes: tubular cell death, inflammation, mitochondrial regulation, and repair/fibrosis. This review aims to clarify how distinct E3 ligases drive or protect against renal damage, and to highlight their diagnostic and therapeutic potential for AKI.