Three highly similar proteins termed NOMO1, NOMO2 and NOMO3, are encoded by a gene mapping to a region of duplication on the p arm of human chromosome 16. All three NOMO proteins share similar functions and have been difficult to characterize individually. NOMO1 (Nodal modulator 1), also known as PM5, is a 1,222 amino acid highly conserved single-pass type I membrane protein expressed in colon tumor tissue and normal colonic mucosa. NOMO proteins are novel antagonists of Nodal signaling which interact with Nicalin to form a Nicalin-NOMO complex, and are rapidly degraded or stabilized by Nicalin. NOMO proteins were once considered candidates for the development of pseudoxanthoma elasticum (PXE), a heritable disorder of connective tissue, as the NOMO genes are located in close proximity to the gene responsible for PXE development (MRP6).