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Anomalous epidermal growth factor receptor (EGFR) signaling plays an important role in the progression of prostate cancer (PCa) and the transformation to castration-resistant PCa (CRPC). A novel tumor suppressor CKLF-like MARVEL transmembrane domain-containing member 5(CMTM5) has a MARVEL domain and may regulate transmembrane signaling. Thus, we postulated that CMTM5 could regulate EGFR and its downstream molecules to affect the biological behaviors of PCa cells. In this study, we found that CMTM5 was expressed in benign prostatic hyper