EBF3 is a transcriptional activator belonging to the Early B-cell Factor family that recognizes palindromic DNA sequences and regulates transcription through RNA polymerase II 1. EBF3 functions as a DNA-binding transcription factor with an atypical zinc-finger and helix-loop-helix domain, which are critical for stabilizing interactions with target DNA sequences 2. Primary Function: EBF3 acts as a transcriptional regulator with dual roles depending on cellular context. In neurodevelopment, EBF3 binds to promoters of neurodevelopmental disorder genes, suggesting roles in neural gene regulation networks 3. In cancer contexts, EBF3 functions as a tumor suppressor by repressing cell growth and migration while activating cell cycle arrest and apoptosis 4. Disease Relevance: Heterozygous loss-of-function variants in EBF3 cause hypotonia, ataxia, and delayed development syndrome (HADDS) and autism spectrum disorders, with symptom severity correlating to variants disrupting the zinc finger domain 2. Both coding and noncoding variants contribute to disease, with coding variants producing more severe HADDS phenotypes compared to noncoding enhancer variants 3. Notably, EBF3 is epigenetically silenced through promoter hypermethylation in gastric carcinoma (40.4% of tissues) and associated with poor prognosis 4, while paradoxically elevated in nasopharyngeal carcinoma metastases where it promotes vimentin expression 5. Clinical Significance: EBF3 serves as an independent prognostic marker in gastric carcinoma, and gene-dosage appears critical for proper neurodevelopment, as demonstrated by duplication/triplication mosaicism cases 6.