In this review, we describe the genetic structure and molecular signaling of OPN and discuss the roles of both OPN and thrombin-cleaved ntOPN as potential biomarkers of several forms of chronic kidney disease (CKD), especially DN, which presents clinically as diabetic kidney disease (DKD), and is the most common cause of CKD and kidney failure [14,15]. This evidence concerns the gene SPP1 and kidney failure.