MERTK, also known as macrophage c-mer tyrosine kinase receptor, is a receptor tyrosine kinase. It belongs to the TAM receptor family, with shared ligands Gas6 and Protein S. MERTK is involved in multiple cellular processes. It promotes apoptotic cell clearance (efferocytosis) in macrophages, skews macrophage polarization towards a pro-tumor M2-like phenotype, and is also associated with pathways such as ERK-TGFβ1, PI3K/AKT, and MAPK/ERK [4,1,2].

In various disease models, MERTK has been shown to play significant roles. In NASH mouse models, holo-or myeloid-specific Mertk targeting decreased liver fibrosis, indicating that macrophage MerTK promotes liver fibrosis [1]. In mouse models of liver, kidney, and lung fibrosis, reducing MERTK expression disrupted the fibrosis-promoting signaling loop and decreased organ fibrosis. Pharmacological inhibition of MERTK also alleviated fibrosis in these models [3]. In melanoma, MerTK+ macrophages accelerated tumor growth, and targeting AhR to suppress MerTK expression improved immunotherapy efficacy [5].

In conclusion, MERTK is crucial in processes like efferocytosis and macrophage polarization. Gene-targeting mouse models, such as KO or CKO models, have revealed its role in fibrotic diseases like NASH-related liver fibrosis and organ-wide fibrosis, as well as in melanoma progression. These findings suggest MERTK as a potential therapeutic target for these diseases.