Compositions and methods for treating pathological calcification and ossification

A method of treating or ameliorating a disease or disorder associated with or caused by an improper serum pyrophosphate (PPi) and phosphate (Pi) balance (PPi/Pi homeostasis) in a subject,

• the method comprising administering to the subject a therapeutically effective amount of a composition comprising a soluble ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) polypeptide or a biologically active fragment, derivative, mutant, or mutant fragment thereof,
• wherein the soluble ENPP1 polypeptide lacks a targeting domain consisting of 4-20 sequential aspartic acid residues,
• wherein the administering increases serum PPi levels in the subject relative to the serum PPi levels in the subject before the administration, and thereby treating or ameliorating the disease or disorder in the subject.