Ehd1, also known as EPS15 Homology Domain containing 1, is a key regulator of intracellular traffic of cell surface receptors. It is involved in endocytic recycling and Golgi to plasma membrane traffic, which are crucial for maintaining the surface expression and downstream signaling of receptors. This function of Ehd1 is important in various biological processes and is associated with several diseases [1,3].

In Ewing sarcoma (EWS), Ehd1 is overexpressed, and high Ehd1 mRNA expression is related to shorter patient survival. ShRNA-knockdown and CRISPR-knockout with mouse Ehd1 rescue experiments showed that Ehd1 is required for tumorigenesis and metastasis. Ehd1 regulates the endocytic recycling and Golgi to plasma membrane traffic of IGF-1R in EWS, and its overexpression-dependent oncogenic traits need IGF-1R expression and kinase activity [1]. In recurrent implantation failure, Ehd1 expression is abnormally elevated in endometrial stromal cells. Ehd1 overexpression inhibits progesterone receptor (PGR) transcriptional activity, promotes the SUMOylation and ubiquitination of progesterone receptor B (PRB), leading to its degradation, thus impairing decidualization. Suppressing Ehd1 expression in HESCs from RIF patients increases the expression of prolactin and insulin-like growth factor-binding protein 1 [2].

In conclusion, Ehd1 is essential for regulating the intracellular traffic of cell surface receptors. Its abnormal expression is associated with diseases like Ewing sarcoma and recurrent implantation failure. The use of gene knockout and rescue models in mice has helped to uncover its role in tumorigenesis, metastasis, and decidualization, providing potential therapeutic targets for these diseases.