NFKBIA and diabetic kidney disease: Smurf2 is the ubiquitin protein ligase of Smad7, which binds to Smad7 and promotes Smad7 degradation; once renal Smad7 is degraded, Smad3 is overactivated, and the TGF-β1/Smad3 signaling pathway is activated, which aggravates inflammatory injury and fibrosis in DKD kidney tissue.[63–65] In addition, Smad7 can negatively regulate NF-κB signaling by inducing IκBα, preventing IκBα degradation, and inhibiting NF-κB signaling-driven inflammatory activation in vitro and in vivo.[66]