MER proto-oncogene tyrosine kinase (MERTK, also called Tyro7 or Eyk) is a TAM-family (Tyro3-Axl-Mer) receptor tyrosine kinase encoded by the human MERTK gene on chromosome 2q14.1. It is a single-pass type I transmembrane receptor with two N-terminal immunoglobulin-like domains, two fibronectin type III repeats, a transmembrane helix and an intracellular tyrosine kinase domain. MERTK is expressed on macrophages, dendritic cells, natural killer cells, retinal pigment epithelial (RPE) cells, Sertoli cells, oligodendrocytes and many tumor cells. Its principal ligands are the vitamin K-dependent proteins Gas6 and Protein S (PROS1), which use their N-terminal Gla domains to bridge phosphatidylserine (PtdSer) exposed on the outer leaflet of apoptotic cells, platelets and photoreceptor outer segments; MERTK also binds Galectin-3, tubby (TUB) and TULP1. Ligand-induced receptor dimerization and autophosphorylation create docking sites that recruit GRB2, PLCG2 (PLC gamma 2), FAK/PTK2, PI3K and DOCK180/Rac1, activating MAPK/ERK, Akt survival and Rac-mediated cytoskeletal reorganization. MERTK is the principal efferocytosis receptor on macrophages and RPE, mediating engulfment of apoptotic cells and photoreceptor outer segments; it also suppresses TLR-driven innate immune activation by inducing STAT1-dependent expression of SOCS1 and SOCS3 (which inhibit TLR and cytokine-receptor signaling), thereby promoting inflammation resolution. The protein is an integral plasma membrane receptor; it can also be shed in soluble form by proteases such as ADAM17.