HES5 (hes family bHLH transcription factor 5) is a transcriptional repressor protein that has important functions in regulating brain development and neurodifferentiation. HES5 works in concert with WNT3A to manage neural progenitor cell fate. It is also dysregulated in a number of cancers; upregulation of HES5 is correlated with proliferation and invasion in non-small cell lung cancer, squamous cervical carcinoma, and hepatocellular carcinoma, while loss of HES5 through epigenetic silencing plays a role in prostate cancer. It is progressively overexpressed in squamous cervical carcinoma and may be a useful marker of poor prognosis for early-stage cancers. In immunohistochemistry, HES5 has nuclear positivity in the brain and testes, with lower levels of expression in the lung, gastrointestinal tract, reproductive organs and a few other tissues throughout the body. References: Int J Gynecol Cancer. 2007 Nov-Dec;17(6):1293-9, PMID: 17388915; Endocr Relat Cancer. 2015 Apr;22(2):131-44, PMID: 25560400; Oncol Rep. 2017 Jan;37(1):474-482, PMID: 27878283; Exp Mol Pathol. 2015 Dec;99(3):474-84, PMID: 26342546; Development. 2004 Nov;131(22):5539-50, PMID: 15496443; Stem Cells Dev. 2014 Jun 15;23(12):1328-39, PMID: 24548083