Isthmin 2 (ISM2) is a member of the Isthmin (ISM) secreted protein family. The ISM family, which also includes ISM1, contains a TSR1 domain followed by an AMOP domain and is involved in diverse developmental and physiological processes [1].

In HPV-infected colorectal cancer, low ISM2 expression was associated with a less advanced clinical stage and better survival outcomes, potentially due to its correlation with a strong tumor immune response [2].

In preeclampsia, the serum concentration of ISM2 protein was decreased, while it was overexpressed in choriocarcinoma, suggesting an angiogenic function for ISM2 in these conditions [3].

In the discovery phase of a study on early esophageal squamous cell carcinoma, autoantibodies targeting ISM2 were identified among other TAAs [4].

In conclusion, ISM2 appears to play important roles in angiogenesis, tumor-related immune response, and potentially in the development of preeclampsia and certain cancers. These findings from different disease-related studies contribute to understanding the biological functions of ISM2, and further in-vivo studies, such as gene knockout (KO) or conditional knockout (CKO) mouse models, could potentially shed more light on its underlying mechanisms in these disease conditions.