GRHL2

GRHL2 (grainyhead-like 2) is a transcription factor encoded by the GRHL2 gene and a member of the grainyhead-like family, which also includes GRHL1 and GRHL3. The GRHL2 protein regulates epithelial development and barrier formation by controlling the expression of genes involved in epithelial differentiation and junctional complexes.

GRHL2 is predominantly expressed in epithelial tissues, including skin and mucosal linings. It promotes epithelial identity by activating promoters of epithelial markers such as E-cadherin (CDH1) and certain tight junction components, while repressing mesenchymal programs. In many experimental models, GRHL2 supports the maintenance of the epithelial state and can suppress epithelial-to-mesenchymal transition (EMT) and invasion; however, context-dependent effects have been reported, with some settings showing pro-survival or proliferative roles.

Developmental and physiological roles include involvement in skin and airway morphogenesis and in organ barrier formation. Mouse and other vertebrate studies indicate GRHL2 is important for proper epithelial differentiation during development and for maintaining barrier integrity in adult tissues.

Dysregulation of GRHL2 has been linked to cancer progression, where epithelial characteristics are often associated with reduced invasiveness, and loss of GRHL2 can promote EMT and metastatic behavior. The gene is also studied as a biomarker of epithelial status and as a potential therapeutic target in certain epithelial-derived cancers.

Genetics and regulation: the GRHL2 gene is located on chromosome 8q22.3 in humans. GRHL2 functions are modulated by signaling pathways and microRNAs, and it interacts with other transcriptional regulators to coordinate epithelial programs.