Fzd4, short for Frizzled-4, is an important receptor for Wnt proteins, which activates several downstream signaling pathways, most notably the Wnt/β -catenin signaling pathway [1,4,5]. This gene is crucial in various biological processes, including the development and maintenance of normal tissues, and its function is associated with stem cell regulation, cell proliferation, and apoptosis [2,4].

In lung cancer, endothelial-specific deletion of FOXF1 in mice decreases Fzd4 expression, which in turn reduces Wnt/β -catenin signaling in tumor-associated endothelial cells (TECs). This leads to decreased pericyte coverage, increased vessel permeability and hypoxia, promoting lung tumor growth and metastasis [1]. In Familial Exudative Vitreoretinopathy (FEVR), whole-gene deletions of Fzd4 have been found in patients, accounting for a certain proportion of cases [3]. Also, in cutaneous squamous cell carcinoma (CSCC), over-expression of Fzd4 in Colo16 cells inhibits cell proliferation and promotes apoptosis, suggesting it may act as a tumor suppressor gene [4].

In conclusion, Fzd4 is essential in maintaining normal physiological functions through its role in Wnt-related signaling pathways. Research using gene-knockout models in mice has revealed its significance in diseases such as lung cancer and FEVR. These findings provide insights into the biological mechanisms underlying these diseases and potential therapeutic targets related to Fzd4.