FKHL15was isolated from a cDNA library enriched for transcripts from 9q22. Isolation and sequencing of a 3.5-kb cDNA clone identified a putative 376-amino-acid protein with greater than 80% homology over a 100-amino-acid stretch to the forkhead DNA-binding domain. TheFKHL15gene contains a region rich in alanine residues, frequently associated with transcriptional repression. The forkhead genes are believed to play important roles in development and differentiation in many different organisms and have also been implicated in the development of some tumors. The map position ofFKHL15on 9q22 places the gene within the candidate regions for the cancer predisposition syndrome multiple self-healing squamous epitheliomata and the degenerative neurological disorder hereditary sensory neuropathy type I. This is a region frequently lost in squamous cell cancer.