Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review)

Emerging insights into lactate‑mediated protein lactylation illuminate novel regulatory axes in the pathogenesis of diabetic nephropathy (DN). While histone lactylation has established epigenetic associations with metabolic memory, expanding proteomic evidence reveals dynamic lactylation landscapes across extracellular matrix components, inflammatory mediators and redox regulators in renal compartments. The present review systematically catalogues DN‑relevant histones and non‑histone substrates undergoing functional lactylation, while mechanistically dissecting how hyperglycemia‑fueled lactate flux drives DN through lactate‑mediated protein modification landscapes. The present review further delineates the progress of research on the potential regulatory mechanisms involved in DN and delve into the possible functions and related mechanisms. This mechanistic reappraisal establishes lactylation topology mapping as a prerequisite for developing precision modulation approaches in DN management.