Protein phosphorylation, catalyzed by protein kinases, is an ancient and essential regulatory mechanism that controls nearly every facet of cellular life. In eukaryotes, most phosphoproteins reside within the cell, confined within the nucleus and cytosol. Nevertheless, secreted proteins such as the milk protein casein and the egg yolk protein phosvitin are also phosphorylated by “orphan” kinases located within the secretory pathway. Indeed, the first evidence alluding to the existence of protein kinases dates back to the nineteenth century when Olof Hammarsten detected phosphorous in casein. Ironically, the kinase that phosphorylates casein, Fam20C, would take nearly 130 years to be identified molecularly. On pages 121–130 of this issue, Vincent Tagliabracci, Lorenzo Pinna and Jack Dixon discuss the history of protein phosphorylation as it pertains to casein and describe a recently identified family of atypical, secreted protein kinases, whose discovery have shed light on several human disorders of biomineralization. Cover image is courtesy of Dan Alexander.