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 diverse functions across different biological processes. In the nervous system, it is involved in synapse formation and microcircuit organization; in the immune system, it may regulate immune cell functions; and it also has potential roles in cell migration, invasion, and angiogenesis [2,3,4,5].

In mouse models, deletion of Igsf8 did not affect steady-state hematopoiesis but significantly improved survival in mouse myeloid leukemia models by depleting leukemia stem cells through enhanced apoptosis and β -catenin degradation [7]. Igsf8 -deficient female mice showed no fertilization defect in vitro or in vivo, indicating it is dispensable for mouse fertility [6]. In preeclampsia, high IGSF8 expression in placental tissues was associated with impaired spiral artery remodeling, and overexpression of IGSF8 in JEG -3 cells inhibited cell migration, invasion, EMT, and HUVEC tube formation [3]. In tumors, IGSF8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells, and an antibody blocking this interaction enhances NK cell killing of malignant cells [1].

In conclusion, IGSF8 plays crucial roles in multiple biological processes such as synapse formation, hematopoiesis, pregnancy-related processes, and tumor-immune interactions. The gene knockout mouse models have provided valuable insights into its functions in myeloid leukemia, fertility, and preeclampsia, highlighting its potential as a therapeutic target in these disease areas.