ELK3 (ETS transcription factor ELK3) is a member of the ETS transcription factor family that functions as both a transcriptional activator and repressor depending on cellular context. ELK3 directly binds to DNA through its ETS domain and regulates target gene expression through multiple mechanisms 1. The protein exhibits dual functionality, acting as a negative regulator under basal conditions but becoming a transcriptional activator when co-expressed with oncogenic signals like Ras or Src. ELK3's transcriptional activity is regulated through post-translational modifications, including phosphorylation-dependent ubiquitination and proteasomal degradation mediated by SPOP 2. The protein's stability is also controlled through m6A-dependent mRNA regulation by FTO 3. ELK3 plays significant roles in cancer progression, promoting cell proliferation, migration, invasion, and chemoresistance across multiple cancer types including T-cell leukemia, prostate cancer, lung cancer, and triple-negative breast cancer 4356. The transcription factor regulates diverse cellular processes including glycolytic metabolism, actin cytoskeleton remodeling, endothelial barrier function, and ferroptosis resistance 3675. Clinically, ELK3 serves as a prognostic biomarker and represents an emerging therapeutic target, with its expression correlating with poor patient outcomes and drug resistance in various malignancies.