Regulatory networks of post-translational modifications in diabetic kidney disease: from pathogenic mechanisms to therapeutic frontiers.

Diabetic kidney disease (DKD) remains a principal microvascular complication of diabetes, driven by a multifaceted pathogenesis that extends beyond pure metabolic dysregulation. Post-translational modifications (PTMs) have emerged as pivotal mechanisms that dynamically regulate protein function and stability under diabetic stress. This review provides a comprehensive synthesis of the regulatory networks governing PTMs in DKD, systematically dissecting the molecular landscapes of phosphorylation, acetylation, ubiquitination, glycosylation, methylation, and SUMOylation. Beyond clarifying individual pathogenic mechanisms, the dysregulation of PTM networks links systemic metabolic disturbances to persistent renal injury. Furthermore, we evaluate emerging therapeutic strategies designed to modulate these modifications. We conclude that targeting PTMs represents a critical advance in DKD therapy, shifting from broad symptomatic management to precise molecular intervention-offering new directions for arresting the progression of DKD.