Conditional GPX4 knockout mice exemplify the risks of single-pathway targeting: while GPX4 deletion in PT cells protects against early AKI by eliminating damaged cells, long-term deletion activates the cGAS–STING pathway—likely via release of fragmented mitochondrial DNA—leading to sustained type I interferon signaling and progressive interstitial fibrosis. This evidence concerns the gene STING1 and acute kidney injury.