Fibroblast growth factor 22 (FGF22) is a member of the FGF7 subfamily that functions as a paracrine factor and was identified in the human placenta in 2001. The FGF22 gene is located on human chromosome 19p13.3, mouse chromosome 10, and zebrafish chromosome 22 and is closely linked to the BSG, HCN2, and POLRMT genes. The gene is composed of three exons, which are common in humans, mice, and zebrafish. However, in humans and mice, FGF22 is produced as two isoforms by alternative splicing, whereas no isoforms have been reported in zebrafish. In humans, FGF22 is expressed in the skin, brain, and ovaries, whereas in mice, it is expressed in the skin, brain, retina, spinal cord, and cochlea. Various abnormalities have been reported in these regions in Fgf22 mutant mice. In zebrafish, fgf22 is expressed in the forebrain, midbrain, and otic vesicles during embryogenesis, and an analysis of knockdown zebrafish models revealed an important role for fgf22 in the process of brain formation. As expected from the results of these functional analyses, FGF22 is also associated with human diseases such as depression, spinal cord injury, hearing loss, and cancer.