Patients with polycystic kidney disease (PKD) are at high risk of developing end-stage renal disease, especially clear cell renal cell carcinoma (ccRCC). Since SET domain-containing 2 (SETD2) has been previously identified as an important tumor suppressor and an immunosuppressor in ccRCC, a recent study aimed to investigate the role of SETD2 in the progression of PKD into ccRCC.