In summary, our study demonstrated that the F727L mutation decreased the glycosylation level of PHEX protein, blocked PHEX protein transport from the ER to the plasma membrane, and reduced its activity to cleave FGF23 into inactive segments, which may explain why the single base substitution c.2179T>C led to the hypophosphatemic rickets in this Chinese family. The gene discussed is FGF23; the disease is hypophosphatemic rickets.