GRHL3

GRHL3 (grainyhead-like transcription factor 3) is a highly conserved transcription factor that regulates epithelial differentiation, epidermal barrier formation, neural tube closure, and craniofacial development during embryogenesis^[1][2]. Mechanistically, GRHL3 functions through transcriptional regulation of downstream target genes involved in epithelial integrity, keratinocyte differentiation, migration, and morphogenetic signaling pathways, making it a central regulator of tissue homeostasis and developmental patterning^[2][3]. In developmental and disease models, GRHL3 controls gene networks associated with skin barrier establishment, oral epithelium formation, lower jaw morphogenesis, and neural tube fusion, while genetic disruption of GRHL3 causes developmental abnormalities including cleft palate and Van der Woude syndrome^[2][4]. GRHL3 is also implicated in epithelial cancers, where it functions predominantly as a tumor suppressor and contributes to maintenance of epithelial identity and inhibition of pathological cellular dedifferentiation^[2]. Compared with related family members GRHL1 and GRHL2, GRHL3 exhibits distinct transcriptional programs despite partial functional redundancy during epidermal morphogenesis and wound repair, highlighting isoform-specific regulation of developmental and disease-associated pathways^[1][4]. Multiple transcript variants encoding distinct GRHL3 isoforms have been identified, and emerging evidence indicates that alternative isoforms may differentially modulate downstream target gene networks, which should be considered when designing mechanistic studies and functional genetic models^[1][3].

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