Igsf8, also known as EWI-2, PGRL, and CD316, is a member of the immunoglobulin superfamily of proteins. It is mainly expressed on cell membranes and has a unique transmembrane structure. Igsf8 has been associated with multiple biological functions, including its role in cell adhesion, synapse formation, and immune regulation. It is involved in pathways related to cell migration, invasion, angiogenesis, and antigen presentation [1-7].

In KO mouse models, deletion of Igsf8 did not affect steady-state hematopoiesis but led to a significant improvement in survival in mouse myeloid leukemia models. It depleted leukemia stem cells through enhanced apoptosis and β -catenin degradation [4]. In the context of preeclampsia, overexpression of Igsf8 in JEG-3 cells inhibited cell migration, invasion, and EMT, as well as impaired angiogenesis [3]. In gliomas, its expression was correlated with the grade and prognosis of the disease, and it may cooperate with immune checkpoints to control the immunological microenvironment [2]. In tumors, Igsf8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells, and blocking this interaction enhances NK cell killing of malignant cells [1].

In conclusion, Igsf8 plays diverse and important roles in various biological processes and disease conditions. The use of Igsf8 KO mouse models has revealed its significance in myeloid leukemia, preeclampsia, gliomas, and tumor immune evasion, providing potential therapeutic targets for these diseases.