ELK4 is an ETS family transcription factor that functions as both a transcriptional activator and repressor through multiple mechanisms. Classically, ELK4 forms a ternary complex with serum response factor (SRF) at DNA regulatory regions, requiring DNA-bound SRF for DNA binding while making extensive contacts to the 5' side of SRF [UniProt]. For transcriptional repression, ELK4 recruits SIRT7 to promoters, facilitating histone H3K18 deacetylation and gene silencing 1. However, in colorectal cancer, ELK4 functions through a noncanonical mechanism, cooperating with transcription factors SP1 and SP3 rather than SRF to activate the pro-angiogenic factor LRG1 2. ELK4 plays significant roles in cancer progression across multiple tumor types. In colorectal cancer, ELK4 phosphorylation by MAPK enhances its interaction with SP1/SP3, promoting tumorigenesis and serving as a poor prognosis marker 2. In gastric cancer, ELK4 knockdown substantially reduces tumor cell proliferation, migration, and invasion 3. ELK4 promotes glioma progression by transcriptionally activating HOMER3, which drives Wnt/β-catenin-mediated epithelial-mesenchymal transition 4, and inhibits melanoma ferroptosis by upregulating CHMP6 expression 5. Conversely, ELK4 exhibits protective roles in inflammatory contexts. In connective tissue disease-associated interstitial lung disease, reduced ELK4 expression promotes M1 macrophage polarization through p38/JNK pathway activation 6. In systemic sclerosis endothelial cells, ELK4 overexpression may ameliorate dysregulated angiogenesis 7. In HPV-transformed cells, ELK4 silencing via miR-129-5p reduces anchorage-independent growth 8.