MEPE is a secreted phosphoglycoprotein that plays a central role in phosphate homeostasis and skeletal mineralization through the PHEX-FGF23-MEPE axis 1. The protein promotes renal phosphate excretion while inhibiting intestinal phosphate absorption, functions mediated by its C-terminal ASARM (acidic serine- and aspartate-rich motif) peptide 2. MEPE also promotes bone and cartilage mineralization by osteoblasts and chondrocytes 2, though elevated MEPE levels paradoxically inhibit mineralization in pathological contexts 3. The ASARM motif is phosphorylated by FAM20C kinase at 31 sites, with all nine serine residues in the ASARM phosphorylated, establishing its functional importance in mineralization 3. MEPE mutations impair bone density 4, and dysregulated MEPE expression contributes to hypophosphatemic rickets disorders. In X-linked hypophosphatemia, loss of PHEX function results in inappropriate MEPE processing and increased circulating FGF23, causing phosphaturia and defective mineralization 5. Under inflammatory conditions simulating biomaterial-associated infection, macrophages upregulate osteocyte MEPE expression, promoting anti-mineralization effects 6. Thus, MEPE functions as a phosphatonin regulating both systemic phosphate balance and local mineralization through phosphorylation-dependent mechanisms.