FAM20C is a Golgi-resident serine/threonine kinase that phosphorylates secretory pathway proteins, primarily within Ser-x-Glu/pSer motifs 1, and constitutes the main kinase for generating the extracellular phosphoproteome 2. In biomineralization, FAM20C phosphorylates FGF23 to direct it toward proteolysis 3, and phosphorylates mineralization-associated proteins including AMELX, AMTN, ENAM, and osteopontin 4. FAM20C also phosphorylates endoplasmic reticulum proteins ERO1A and P4HB, regulating ER redox homeostasis and proteostasis during stress conditions 5. Loss-of-function FAM20C variants cause Raine syndrome, presenting as either lethal osteosclerotic dysplasia with intracerebral calcifications and atherosclerosis, or non-lethal hypophosphatemic rickets 46. Beyond skeletal disease, FAM20C facilitates cancer progression—it enhances breast cancer metastasis 7 and mediates invasive growth of radial glial stem-like cells in gliomas 8, with epigenetic upregulation of FAM20C promoting glioma proliferation and metastasis 9. FAM20C also participates in lipid homeostasis, wound healing, and cell migration 2, making it a multifunctional kinase with both developmental and pathological significance.