GABPA is a sequence-specific DNA-binding transcription factor that activates RNA polymerase II-dependent gene expression 1. As an ETS family member, GABPA regulates distinct gene networks controlling cellular processes including migration through direct targets like RAC1 and KIF20A 1. In mitochondrial bioenergetics, GABPA cooperates with PGC-1α and other transcription factors to potentiate expression of tricarboxylic acid cycle genes essential for cardiac ATP production 2. GABPA also functions as a tumor suppressor in renal cell carcinoma by activating TGFBR2 to engage TGFβ signaling and promote ferroptosis through ACSL4, processes disrupted by oncometabolite-induced methylation 34. In hepatocellular carcinoma, GABPA binds the TERT promoter to regulate telomerase expression; correcting TERT promoter mutations impairs GABPA binding and suppresses tumorigenesis 5. GABPA expression is downregulated in cancer tissues and associated with poor survival; its restoration via demethylation or pathway modulation represents therapeutic potential 34. Additionally, GABPA regulates squalene epoxidase transcription in bladder cancer, where its inhibition induces oxidative stress and apoptosis 6. Sex-dimorphic DNA methylation of GABPA occurs in first trimester placenta with potential implications for fetal development 7.