ELK4 is an ETS-domain transcription factor that functions as both a transcriptional activator and repressor. It forms a ternary complex with serum response factor (SRF) at target promoters, making extensive DNA contacts while requiring DNA-bound SRF for complex formation. ELK4 also interacts with SIRT7 to recruit and stabilize this deacetylase at promoters, leading to histone H3 lysine-18 deacetylation and transcriptional repression. ELK4 drives oncogenic transcriptional programs across multiple cancer types. In colorectal cancer, ELK4 cooperates with transcription factors SP1 and SP3—rather than the canonical SRF partner—to activate the neoangiogenic factor LRG1, promoting tumorigenesis 1. In gastric cancer, ELK4 knockdown substantially reduces tumor cell proliferation, migration, and invasion 2. ELK4 also promotes glioma progression by upregulating HOMER3, which activates Wnt/β-catenin signaling and epithelial-mesenchymal transition 3, and enhances melanoma cell proliferation while suppressing ferroptosis through CHMP6 upregulation 4. In HPV-associated cervical cancer, ELK4 drives cell cycle progression and stem cell-like properties via the FBXO22/PTEN axis 5. Clinically, ELK4 represents a candidate therapeutic target. In colorectal cancer, combining MEK/ERK inhibitors with the SP1 inhibitor mithramycin A produces synergistic antitumor effects by disrupting the ELK4-SP1/SP3 complex 1. ELK4 serves as a marker of poor prognosis in colorectal cancer.