Proto-oncogene tyrosine-protein kinase MER (MERTK)

Proto-oncogene tyrosine-protein kinase MER (MERTK) is a member of the TAM (Tyro3, Axl, Mer) family of receptor tyrosine kinases that plays a critical role in the phagocytic clearance of apoptotic cells, a process known as efferocytosis (UniProt Q12866). It is essential for maintaining immune homeostasis and preventing autoimmunity by promoting an anti-inflammatory environment through the suppression of toll-like receptor signaling (PubMed: 28249987). In the retina, MERTK is vital for the health of the retinal pigment epithelium, and mutations in the gene are a known cause of retinitis pigmentosa (NCBI Gene: 10461). In oncology, MERTK is frequently overexpressed or activated in various malignancies, including leukemia, melanoma, and non-small cell lung cancer, where it contributes to tumor cell survival, chemoresistance, and immune evasion by polarizing macrophages toward a pro-tumor M2 phenotype (PubMed: 30206134). Consequently, MERTK has become a high-interest therapeutic target for small molecule inhibitors and monoclonal antibodies aimed at restoring anti-tumor immunity and enhancing the efficacy of standard chemotherapies or checkpoint inhibitors. Clinical challenges include managing potential off-target effects on the retina, given MERTK's indispensable role in visual cycle maintenance (PubMed: 25184291).

Other names

c-merMER receptor tyrosine kinaseTyrosine-protein kinase MerSTK kinaseRP38TAM receptor

Small molecule kinase inhibitors (ATP-competitive inhibition); Monoclonal antibodies (ligand blocking or receptor internalization)