Tspan4, a tetraspanin protein, is a key regulator of migrasome formation [4,5,6]. Migrasomes are extracellular vesicles related to cell migration. Tspan4 may be involved in multiple biological processes such as cell migration, proliferation, and intercellular communication, potentially through its role in migrasome-related functions. The TGF-β1/Smad2/3 signaling pathway can induce Tspan4 expression and migrasome production [1].

In various disease contexts, Tspan4 shows significant associations. In proliferative vitreoretinopathy (PVR), Tspan4-positive migrasomes derived from retinal pigmented epithelium cells contribute to PVR development. TGF-β1 increases Tspan4 expression, leading to migrasome production, which can enhance the migration and proliferation of retinal pigmented epithelium cells. Inhibiting Tspan4 in these cells reduces the ability to initiate experimental PVR [1]. In glioblastoma (GBM), Tspan4 promotes GBM progression by interacting with epidermal growth factor receptor (EGFR) and regulating its stability. Knocking down Tspan4 inhibits GBM cell proliferation, invasion in vitro, and tumorigenicity in vivo [2]. Tspan4 is also associated with atherosclerosis and pan-cancer. Its expression is upregulated in foam cells from patients with atherosclerosis and is related to poor prognosis. In pan-cancer, Tspan4 expression differs among immune subtypes and can serve as a diagnostic and prognostic target, especially in glioblastoma multiforme where it is an independent risk factor [3].

In conclusion, Tspan4 is crucial for migrasome-mediated biological processes. Studies, including those using gene-knockdown models, have revealed its significant roles in diseases such as PVR, glioblastoma, atherosclerosis, and pan-cancer. Understanding Tspan4's functions provides potential therapeutic targets for these diseases.