Homeodomain (HD) genes are helix-turn-helix transcription factors that play key roles in the specification of cell fates. OTP (orthopedia homeobox) is a 325 amino acid nuclear protein belonging to the paired homeobox family and Bicoid subfamily. OTP is expressed in neurons, which give rise to the paraventricular (PVN), supraoptic (SON), anterior periventricular (aPV) and arcuate (ARN) nuclei. Containing a homeobox DNA-binding domain and a OAR domain, OTP is suggested to be involved in the differentiation of hypothalamic neuroendocrine cells. At early embryonic stages in mice, the expression of SIM2 is downregulated in the absence of OTP, indicating a potential role for OTP as an upstream regulator of SIM2. OTP is highly conserved in evolution and is encoded by a gene located on human chromosome 5, which contains 181 million base pairs and comprises nearly 6% of the human genome.