In this study, we revealed the increased expression of USP36 in high glucose-induced renal tubular cell injury both in vitro and in vivo, and the role of USP36 overexpression in DKD is related to its deubiquitination effect of DOCK4, that could activate Wnt/β-catenin signaling pathway and mediate EMT. The gene discussed is DOCK4; the disease is diabetic kidney disease.