GRHL1 (grainyhead like transcription factor 1) is a transcription factor that plays diverse roles in cellular differentiation, development, and disease. In normal physiology, GRHL1 functions as a pro-differentiation factor that is activated by glucose binding, which enables IRF6 dimerization and subsequent induction of GRHL1 and other differentiation-promoting transcription factors during epidermal development 1. The protein exhibits context-dependent tumor suppressor or oncogenic functions. In neuroblastoma, GRHL1 acts as a tumor suppressor, with high expression correlating with favorable patient survival and inhibiting proliferation and colony formation 2. MYCN and HDAC3 negatively regulate GRHL1 transcription in neuroblastoma cells 2. Conversely, in lung cancer, GRHL1 promotes cell cycle progression by upregulating cell cycle-related genes through direct transcriptional activation 3. EGFR-ERK signaling activates GRHL1 via phosphorylation at Ser76, promoting its nuclear translocation in lung cancer cells 3. GRHL1 also serves as a potential biomarker, with elevated circulating levels showing predictive value for non-small-cell lung cancer detection in elderly patients 4. Additionally, GRHL1 gene rearrangements, particularly FOXK1::GRHL1/2 and GPS2::GRHL1/2/3 fusions, represent oncogenic drivers in trichogerminoma 5. In placental tissue, GRHL1 functions as a hub gene in networks associated with fetal growth regulation 6.