CREBRF (CREB3 regulatory factor) functions as a negative regulator of endoplasmic reticulum stress response and the unfolded protein response (UPR) by repressing CREB3 transcriptional activity 1. The gene encodes a DNA-binding transcription factor that recruits CREB3 into nuclear foci and regulates RNA polymerase II-mediated transcription. Mechanistically, CREBRF modulates multiple cellular pathways including ER stress, cell cycle regulation, and autophagy 1. In cancer contexts, CREBRF promotes cell proliferation through AKT signaling pathway activation, with CREBRF silencing inducing G1/S phase cell cycle arrest in gastric cancer cells 2. CREBRF also influences cervical cancer progression via the miR-545-3p/CREBRF regulatory axis 3. Disease relevance extends to metabolic disorders and cancer. CREBRF variants (rs12513649 and rs373863828) show paradoxical associations in Polynesian and Pacific Islander populations: the protective alleles associate with increased BMI and reduced type 2 diabetes risk, plus greater adult height 456. Large-scale lipid GWAS identified CREBRF as a prioritized gene with convergent functional evidence supporting its role in lipid biology 7. Clinically, CREBRF emerges as a potential therapeutic target in cancer treatment given its roles in tumor proliferation and survival pathways.