Tmem64, a transmembrane protein, has been implicated in multiple biological functions. It is involved in the regulation of calcium signaling and is associated with the Wnt/β -catenin signaling pathway, playing a role in processes such as cell differentiation, proliferation, and apoptosis, which are crucial for normal physiological function and disease development [1,3,4,5]. Genetic models, like KO mouse models, have been instrumental in studying its functions.

In glioma, Tmem64 is highly expressed compared to normal tissues, and its high expression correlates with higher grade and worse prognosis. Loss-and gain-of-function studies show it enhances cell proliferation, tumorigenicity, and inhibits apoptosis by activating the Wnt/β -catenin signaling pathway [1]. In hepatocellular carcinoma, high Tmem64 expression is an independent risk factor for poor prognosis and promotes cell proliferation, migration, and invasion [2]. Tmem64-deficient mice exhibit increased bone mass due to impaired osteoclast formation as it modulates calcium signaling during osteoclastogenesis [3]. Ablation of Tmem64 in mice leads to increased osteoblast and reduced adipocyte differentiation, while overexpression has the opposite effect, indicating its role in mesenchymal lineage allocation through modulating Wnt/β -catenin signaling [4]. In prostate cancer, Tmem64 is involved in metastatic progression by regulating Wnt3a secretion [5].

In conclusion, Tmem64 plays essential roles in cell-related biological processes like differentiation, proliferation, and apoptosis. The use of KO mouse models has revealed its significance in diseases such as glioma, hepatocellular carcinoma, osteoporosis-related bone metabolism, and prostate cancer, providing potential insights for diagnosis and treatment in these disease areas.