CDKN2B is known to be a tumor suppressor gene, and is a potential effector of the TGF-beta induced cell cycle arrest. The gene codes for a protein, p15, which is an inhibitor of cyclin dependent kinases, and thus, acts as a negative regulator of cell proliferation. p15 interacts strongly with cyclin-dependent kinases CDK4 and CDK6, and inhibits their ability to interact with cyclins D, thereby blocking the CyclinD/CDK complex from phosphorylating the retinobloastoma protein (RB1). This induces cell cycle arrest at the G1 checkpoint, and prevents transition of the cell cycle into the S phase. Mutations in the gene cause the protein to lose their capacity to block the Cyclin D/CDK activation, resulting in uncontrolled cell proliferations, and development of malignancies. Apart from mutations, hypermethylation of the gene has also been shown to cause inactivation in some cancers. Moreover, mutations in the gene have been shown to cause retinoblastoma, T-cell acute leukemia, meningiomas, neoplasms, and other primary tumors.