Mathur et al. found that high glucose exposure in DKD models upregulated pleckstrin homology domain leucine-rich repeat protein phosphatases 1 (PHLPP1) and promoted the nuclear retention of forkhead box protein O1 (FoxO1) through double minute 2 protein (MDM2), thus leading to aberration in renal gluconeogenesis and activation of the apoptotic cascade. Here, MDM2 is linked to diabetic kidney disease.