Epor, the erythropoietin receptor, is a member of the cytokine class I receptor family. It classically mediates erythropoietin (EPO)-induced erythroblast proliferation and differentiation, which is crucial for erythropoiesis to secure oxygen transport and control plasma viscosity [1]. Epor activation also leads to Jak2-dependent phosphorylation of tyrosine residue 88 of p27Kip1, converting it from a CDK-inhibitor to an activator and assembly factor of CDK4,6, thus promoting erythroid progenitor proliferation [1].

In mice, conditional deletion of Epor in the monocytic lineage reduces EPO-induced bone loss, suggesting that Epor in this lineage is at least partially responsible for EPO's effect on bone mass [2]. Deletion of Epor in osteoprogenitor cells increases vertebral bone volume in female mice, indicating that Epor in osteoprogenitors is essential in regulating osteoblast function and osteoblast-mediated osteoclastogenesis via the RANKL/OPG axis [3]. Myeloid-specific Epor-deficient mice display restrained M2 macrophage polarization and impaired inflammation resolution in acute lung injury, showing that Epor signaling in macrophages is important for proper macrophage polarization [4].

In conclusion, Epor is essential for erythropoiesis, bone homeostasis, and macrophage polarization. Gene-knockout mouse models, especially conditional knockout models, have been instrumental in revealing Epor's role in these biological processes. Understanding Epor's function provides insights into diseases related to erythropoiesis, bone health, and inflammation [1,2,3,4].