Tspan9, also known as NET-5 and PP1057, is a member of the transmembrane 4 superfamily (TM4SF) of tetraspanins. Tetraspanins are four-transmembrane proteins that can recruit other cell surface receptors and signaling proteins into microdomains, regulating various cellular functions. Tspan9 has been implicated in multiple biological processes and disease-related pathways, such as its role in platelet activation by regulating the lateral diffusion of the collagen receptor GPVI [3]. It is also involved in virus-host interactions, modulating the early endosome compartment to facilitate membrane fusion of certain viruses [5].

In osteosarcoma, Tspan9 is upregulated. Knockdown of Tspan9 suppresses cell migration, invasion, and epithelial-mesenchymal transition (EMT), while overexpression has the opposite effects. Tspan9 promotes osteosarcoma metastasis via activating the FAK-Ras-ERK1/2 pathway [1].

In gastric cancer, Tspan9's role seems complex. In some studies, its overexpression promotes autophagy and suppresses chemosensitivity to 5-fluorouracil [2], while in SGC7901 cells, overexpression inhibits proliferation, migration, and invasion through the ERK1/2 pathway [6]. Also, in gastric cancer, lower Tspan9 expression in cancer samples is associated with a poorer prognosis [7].

In hepatocellular carcinoma, Tspan9 is downregulated, and its downregulation is related to poor prognosis and tumor immune infiltration [4].

In conclusion, Tspan9 plays diverse and context-dependent roles in various biological processes and diseases. Studies, especially those using gene-knockdown or knockout models in cells and potentially in mice (although direct mouse KO/CKO model details are not overly abundant in the provided references), have revealed its significance in cancer metastasis, drug resistance, and immune-related processes. Understanding Tspan9's functions could potentially lead to new therapeutic strategies for diseases like osteosarcoma and gastric cancer.