In cancer cells, cyclin D–CDK4/6-dependent phosphorylation of speckle-type POZ protein (SPOP)/Cullin-3 ubiquitin ligase complex destabilizes PD-L1 via proteasome-mediated degradation, but inhibition of CDK4/6 significantly elevates PD-L1 level25. The gene discussed is CUL3; the disease is cancer.