Mer

Mer/MERTK is a TAM receptor tyrosine kinase activated by Gas6 and protein S, linking apoptotic-cell recognition to inflammation, hemostasis, survival, adhesion, and migration^[1]. Mechanistically, Mer supports efferocytosis because Gas6 and protein S bind apoptotic cells and enable TAM-dependent phagocytosis and receptor phosphorylation^[2]. Mer signaling connects this recognition step to Src-FAK^Tyr861^-p130^CAS^/CrkII/Dock180-Rac1 activation, thereby promoting lamellipodia formation and apoptotic-cell engulfment^[3]. In human macrophage models, MerTK blockade uniformly suppresses apoptotic-cell uptake, while Axl blockade affects poly(I:C)-stimulated macrophages but not resting macrophages, distinguishing Mer from Axl in baseline efferocytosis^[4]. In retinal pigment epithelium models, Mertk triggers photoreceptor outer-segment ingestion, and MERTK-mutant patient iPSC-RPE cells show reduced outer-segment internalization, supporting retinitis pigmentosa disease modeling^[5]. Compared with related TAM isoforms, Mer is described as uniquely capable of tethering apoptotic cells to macrophages and driving their internalization^[2]. For experimental applications, MRX-2843 inhibits MERTK and FLT3 activation, induces apoptosis in AML models, and prolongs survival in xenografts^[6]. MerTK ASO reduces MerTK in tumor-associated macrophages and improves immunoradiotherapy efficacy in mouse tumor models^[7].