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 been implicated in various biological processes. It can interact with tetraspanin molecules like CD9 and CD81, and is involved in pathways related to cell adhesion, migration, and immune regulation. Its expression is important in the development of the nervous system, organ epithelia, and has potential significance in cancer and other diseases [2,5,6].

Deletion of Igsf8 did not affect steady state hematopoiesis, but it led to a significant improvement of survival in mouse myeloid leukemia models by depleting leukemia stem cells through enhanced apoptosis and β -catenin degradation. Igsf8 -deficient female mice showed no fertilization defect in vitro or in vivo, indicating it is dispensable for mouse fertility. In preeclampsia, high IGSF8 expression in placental tissues was associated with impaired trophoblast cell migration, invasion, and angiogenesis [3,4,1].

In conclusion, IGSF8 plays diverse roles in biological processes such as neural development, reproduction, and cancer-related mechanisms. Gene knockout mouse models have been crucial in revealing its functions in myeloid leukemia, fertility, and preeclampsia, providing insights into potential therapeutic targets for these diseases.