In summary, our findings shed light on the evidence that pharmacological or genetic interruption of NETs formation synergizes with Fn14 mAb to prevent septic AKI by restoring the infiltration and survival of efferocytic GAS6+ macrophages and augmenting the tubular cell-intrinsic Fn14 transcription through dismantling the proteasomes-mediated turnover of HOXA5. This evidence concerns the gene HOXA5 and acute kidney injury.