The present invention includes compositions and methods for treating and/or preventing renal and/or kidney stones in a human subject. In certain embodiments, the subject is administered certain ENPP1 polypeptides or ENPP3 polypeptides, mutants, or mutant fragments thereof.

In certain aspects, the present invention provides novel soluble ENPP1 or ENPP3 polypeptides, as well as compositions and methods for using those variants to treat an indication associated an ENPP1 or ENPP3 deficiency. The compositions and methods provided herein are useful in treating diseases associated with an ENPP1 or ENPP3 deficiency such as pathological calcification or pathological ossification.

The present invention provides a method of treating NPP1 deficiency or NPP1-associated disease such as idiopathic infantile arterial calcification (IIAC), pseudoxanthoma elasticum, vascular calcification in chronic kidney disease (VCCKD), insulin resistance, hypophosphatemic rickets, myocardial ischemia, joint calcification, angioid streaks, and ossification of the posterior longitudinal ligament of the spine. The present invention provides a method for treating tissue calcification by administering soluble NPP1 to produce a transient increase in serum pyrophosphate levels.

The present disclosure provides compositions and methods for treating Peripheral Artery Diseases in a subject by administering an ectonucleotide pyrophosphatase phosphodiesterase-1 (ENPP1) agent or an ectonucleotide pyrophosphatase phosphodiesterase-3 (ENPP3).

The present invention includes compositions and methods for treating stroke in sickle cell anemia (SCA) patients. In certain embodiments, the patient is administered certain ENPP1- or ENNP3-containing polypeptides, mutants, or mutant fragments thereof.

The present invention includes compositions and methods for treating disease and disorders associated with pathological calcification or pathological ossification by modulating the level or activity of NPP1 or a mutant thereof, or a mutant NPP4 modified to exhibit ATP hydrolase activity similar to the hydrolase activity of NPP1.

The present invention relates to compositions and methods for modulating coagulation through modulating the level or activity of ENPP4.

The present invention provides a method for producing a target substance, the biosynthetic pathway of which is ATP-dependent, such as, for example, amino acids, nucleosides, nucleotides, isoprenoids, and peptides, by fermentation of a bacterium which has been modified to overexpress a gene encoding a protein having H.sup.+-translocating membrane-bound pyrophosphatase activity, such as, for example, the hppA gene native to R. rubrum or a variant thereof.

The present disclosure provides, among other things, vectors for expression of ENPP1 or ENPP3 in vivo and methods for the treatment of diseases of calcification and ossification in a subject.

The present invention includes compositions and methods for treating disease and disorders associated with pathological calcification or pathological ossification.