CREBZF is a CREB/ATF bZIP transcription factor that plays crucial roles in metabolic regulation, stress responses, and disease pathogenesis. The protein functions as a metabolic regulator in adipose tissue, where it promotes inflammatory responses in macrophages that contribute to insulin resistance and type 2 diabetes by competitively inhibiting IκBα binding to p65, enhancing NF-κB activity 1. In thermogenesis regulation, CREBZF undergoes glucose-induced acetylation at Lys208 by CBP/p300 and HDAC3, which stabilizes the protein and allows it to associate with PGC-1α to repress thermogenic gene expression 2. CREBZF also serves as a critical checkpoint in liver disease progression, promoting hepatocyte injury and NASH development by stimulating osteopontin production through miR-6964-3p inhibition 3. The transcription factor responds to amino acid deprivation through an AARE-like element in its promoter 4 and functions as a positive regulator of p53 tumor suppressor activity, stabilizing p53 through post-translational modifications 5. CREBZF expression is dysregulated in various cancers, where it can suppress breast cancer progression through feedback loops involving circPAPD4 6 and is targeted by miRNAs in gastric cancer 7.