The zinc-finger protein 516 (ZNF516) is a transcription repressor and a potential suppressor of EGFR. ZNF516 is physically associated with the CtBP/LSD1/CoREST complex and transcriptionally represses a cohort of genes including EGFR that are critically involved in cell proliferation and motility. In breast cancer cells, ZNF516 represses EGFR transcription through the interaction with the CtBP/LSD1/CoREST complex. ZNF516 may serve as a potential therapeutic target for breast cancer.