In addition, natural bioactive compounds and nanodelivery systems can selectively modulate ABCA1/G1-mediated cholesterol efflux, attenuating lipid accumulation.In conclusion, this study highlights the pivotal role of macrophage cholesterol efflux in DKD pathogenesis beyond traditional metabolic factors and proposes novel MCE-targeted therapeutic strategies, offering new insights for the prevention and treatment of DKD. Here, ABCA1 is linked to diabetic kidney disease.