Diabetic nephropathy (DN) is a well-known microvascular complication in patients with diabetes mellitus, which is characterized by the accumulation of extracellular matrix in the glomerular and tubulointerstitial compartments, along with the hyalinization of intrarenal vasculature. DN has recently emerged as a leading cause of chronic and end-stage renal disease. While the pathobiology of other diabetic microvascular complications, such as retinopathy, is largely understood and has reasonable therapeutic options, the mechanisms and management strategies for DN remain incompletely elucidated. In this editorial, we comment on the article by Liu et al, focusing on the mechanisms underlying the detrimental impact of β-arrestin-2 on the kidneys in the context of DN. The authors suggest that inhibiting β-arrestin-2 could alleviate renal damage through suppressing apoptosis of glomerular endothelial cells (GENCs), highlighting β-arrestin-2 as a promising therapeutic target for DN. The study proposed that β-arrestin-2 triggers endoplasmic reticulum (ER) stress via the ATF6 signaling pathway, thereby promoting GENC apoptosis and exacerbating DN progression. Given the novel and crucial role of β-arrestin-2 in ER stress-related DN, it is imperative to further explore β-arrestin-2, its roles in ER stress and the potential therapeutic implications in DN.

• Diabetes mellitus
• Diabetic nephropathy
• β-arrestin-2
• Endoplasmic reticulum stress
• ATF6 signaling pathway

• Diabetic nephropathy
• Metabolic regulation
• Multi-target therapies
• Therapeutic strategies
• Tissue-specific signaling
• Type 2 diabetes
• β-arrestin 1
• β-arrestin 2