Fam20C is a Golgi kinase phosphorylating the majority of the secreted proteins. In this decade, the roles of Fam20C has been largely disclosed in the loss-of function models. How the influence of the over-expressed Fam20C on cells or organs, and whether Fam20C was associated to tumorogensis still remain unknown. In the latest publication in Bioscience Reports, a group from the second affiliated hospital of Harbin Medical University established a correlation between the elevated Fam20C expression and the poor prognosis of multiple cancers. In addition, they also proposed the potential mechanisms how the increased Fam20C expression played a detrimental role in tumor progression by suggesting that the up-regulated Fam20C level impacted the infiltration of immune cells and the capability of cancer metastasism. To give an overview of the expanding knowledge of Fam20C involved in the physiological and pathological events, we first reviewed the history of Fam20C studies in this commentary, then, evaluated the correlation of the elevated Fam20C expression to the prognosis of multiple cancers, and finally, interpreted the perspectives that the Fam20C gain-of-function model was also critical for cancer therapy.

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