Meanwhile, CMTM6 also fulfills a similar role in the immunological synapse between T cells and cancer cells or APCs.513 Another family member CMTM4 was responsible for the positive regulation of PD-L1 expression in CMTM6 deficient cells.514 The cyclin-dependent kinase 4 (CDK4) phosphorylates SPOP, the E3-ubiquitin ligase of PD-L1, and stabilizes SPOP by dissociating it from the ubiquitin E3-ligase complex APC/CCdh1. This evidence concerns the gene CDK4 and cancer.