With established links to human skeletal diseases, the initial roles of the Fam20 family were thought to be focused on biomineralization; however, identification of SxE/pS motifs in over two-thirds of all secreted phosphoproteome including plasma, serum, cerebrospinal fluid, neuropeptides, and extracellular matrix components points to a diverse function of Fam20C. This evidence concerns the gene FAM20C and bone disorder.