Tyrosine-protein kinase receptor MERTK (MERTK)

Tyrosine-protein kinase receptor MERTK is a member of the TAM (Tyro3, Axl, Mer) family of receptor tyrosine kinases, primarily known for its critical role in efferocytosis, the process by which phagocytes remove apoptotic cells. In a healthy physiological state, MERTK signaling promotes an anti-inflammatory environment and maintains tissue homeostasis, particularly in the retina and immune system. However, in the context of oncology, MERTK is frequently overexpressed or overactive, acting as an 'immune checkpoint' that allows tumors to evade the immune system by suppressing T-cell activation and promoting an immunosuppressive microenvironment. Beyond cancer, mutations in the MERTK gene are a known cause of autosomal recessive retinitis pigmentosa due to the failure of retinal pigment epithelial cells to phagocytose shed photoreceptor outer segments. Therapeutic strategies currently focus on small molecule inhibitors and monoclonal antibodies to block MERTK signaling in cancer, though drug development must carefully manage the risk of retinal toxicity. MERTK's dual role as a promoter of cell survival in tumors and a vital homeostatic regulator in the eye makes it a complex but promising therapeutic target.

Other names

MERc-merProto-oncogene c-MerReceptor tyrosine kinase MerTKSTKRP38Tyrosine-protein kinase Mer

Small molecule inhibition of the intracellular kinase domain to block downstream signaling; Monoclonal antibodies to block ligand binding (Gas6/Protein S) or induce receptor internalization.