Genetic ablation of Cbl-b or targeted inactivation of its E3 ligase activity does not affect NK cell development but renders NK cells hyper-responsive to activation and capable of spontaneously rejecting metastatic tumors.172 Mechanistically, Cbl-b functions in the pathway of the TAM family of receptor tyrosine kinases, including Tyro3, Axl, and Mer, known to inhibit NK cell function. The gene discussed is CBLB; the disease is metastatic neoplasm.