Canopy FGF signaling regulator 2 (CNPY2) is a FGF21-modulated protein containing a saposin B-type domain. In vitro studies have shown CNPY2 is able to enhance neurite outgrowth in neurons and stabilize the expression of low density lipoprotein receptor in macrophages and hepatocytes. However, no in vivo data are available on the normal expression of CNPY2 and information is lacking on which cell types express this protein in tissues. To address this, the present study examined CNPY2 expression at the mRNA and protein levels. Quantitative PCR and ELISA examination of mouse tissues showed that CNPY2 varies between organs, with the highest expression in the heart, lung and liver. Immunohistochemistry detected CNPY2 in a variety of cell types including skeletal, cardiac and smooth muscle myocytes, endothelial cells and epithelial cells. CNPY2 was also detectable in mouse blood and human and mouse uteri. These data demonstrate CNPY2 is widely distributed in tissues and suggest the protein has biological functions that have yet to be identified. Using these new observations we discuss possible functions of the protein.