We have cloned a new member of the granin family, termed human secretogranin III (SgIII), that encodes 468 amino acid residues. The human SgIII protein possesses an N-terminal signal peptide, seven dibasic sites, and the repeated DSTK sequences. These structure characteristics are similar to other members of secretogranin family. The human SgIII has homologous proteins in mouse, rat, and Xenopus laevis. Genomic organization shows the gene includes 12 coding exons spanning 39 kb of genomic DNA on the human chromosome 15. Human SgIII is expressed widely as showed in Northern blot and its cDNA hybridizes to 2.2 kb and 1.9 kb bands in many tissues, with two additional 4.5 kb and 3.3 kb bands in brain. Subcelluar localization and immunoblotting indicated SgIII was secreted out of cell through trans-Golgi network (TGN). SgIII may take effect in the biogenesis of secretory granules as a helper protein and be involved in the production or release of peptide hormones in the regulated secretory pathway.