Abstract:Sepsis-associated acute kidney injury（SA-AKI）is a frequently encountered critical-care syndrome that complicates 40%-50% of sepsis cases and carries a markedly higher mortality than sepsis alone，representing a major threat to human health. Zinc finger protein A20，also known as tumor necrosis factor alpha-induced protein 3（TNFAIP3），is an important ubiquitin-editing enzyme. It was originally identified as a gene induced by tumor necrosis factor alpha and can negatively regulate the nuclear factor-κB（NF-κB）signaling pathway，serving as a key“brake”molecule in cell death and inflammatory responses. A20 encoded by the TNFAIP3 gene is a key negative regulator of inflammation, which is essential for regulating cell apoptosis and suppressing inflammatory cascades. Its protective role in SA-AKI is increasingly recognized. This review delineates the structural features，and biological functions，expression regulation of A20 ，summarizes current mechanistic insights into its renoprotective actions in SA-AKI ，and outlines emerging A20-targeted therapeutic strategies together with their prospects for clinical translation，aiming to provide novel therapeutic avenues for SA-AKI.