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 biomineral