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

The present invention provides a novel fusion polypeptide containing a catalytic domain of NPP1 fused to a targeting moiety, nucleic acids encoding the fusion polypeptide, a vector containing the nucleic acid integrated thereinto, a host cell transformed with the vector and pharmaceutical compositions comprising the fusion polypeptide.

The purpose of the present invention is to provide an agent for improving intestinal flora, the agent being capable of improving intestinal flora by increasing the number of bacteria belonging to the genus Bifidobacterium and/or the genus Lactobacillus in the intestines. In the present invention, an enzyme-containing substance derived from fungi belonging to the genus Penicillium increases the number of both bacteria belonging to the genus Bifidobacterium and bacteria belonging to the genus Lactobacillus in the intestines, and is capable of exhibiting the excellent effect of improving the intestinal flora.

The present disclosure provides, in one aspect, specific doses of an ENPP1 agent for in vivo treatment of Diffuse idiopathic skeletal hyperostosis (DISH), Ankylosing Spondylitis, and/or Spondylarthritis.

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.