TAM (TYRO3, AXL, and MERTK) protein tyrosine kinase membrane receptors and their vitamin K-dependent ligands GAS6 and protein S (PROS) are well-known players in tumor biology and autoimmune diseases. In contrast, TAM regulation of fibrogenesis and the inflammation mechanisms underlying metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and, ultimately, liver cancer has recently been revealed. GAS6 and PROS binding to phosphatidylserine exposed in outer membranes of apoptotic cells links TAMs, particularly MERTK, with hepatocellular damage. In addition, AXL and MERTK regulate the development of liver fibrosis and inflammation in chronic liver diseases. Acute hepatic injury is also mediated by the TAM system, as recent data regarding acetaminophen toxicity and acute-on-chronic liver failure have uncovered. Soluble TAM-related proteins, mainly released from activated macrophages and hepatic stellate cells after hepatic deterioration, are proposed as early serum markers for disease progression. In conclusion, the TAM system is becoming an interesting pharmacological target in liver pathology and a focus of future biomedical research in this field.

TAM（TYRO3、AXL 和 MERTK）蛋白酪氨酸激酶膜受体及其维生素 K 依赖性配体 GAS6 和蛋白 S (PROS) 是肿瘤生物学和自身免疫性疾病中的知名参与者。相比之下，TAM 对纤维发生的调节以及代谢功能障碍相关脂肪性肝炎 (MASH)、肝硬化以及最终肝癌的炎症机制最近已被揭示。 GAS6 和 PROS 与凋亡细胞外膜中暴露的磷脂酰丝氨酸结合，将 TAM（尤其是 MERTK）与肝细胞损伤联系起来。此外，AXL 和 MERTK 调节慢性肝病中肝纤维化和炎症的发展。最近关于对乙酰氨基酚毒性和慢加急性肝衰竭的数据表明，急性肝损伤也是由 TAM 系统介导的。可溶性 TAM 相关蛋白主要由肝脏恶化后活化的巨噬细胞和肝星状细胞释放，被提议作为疾病进展的早期血清标志物。总之，TAM系统正在成为肝脏病理学中一个有趣的药理学靶点，也是该领域未来生物医学研究的焦点。