Our findings focused on the ABCC5-mediated enzalutamide resistance and indicated that ABCC5 regulates the activity of NF-κB-p65 and generation of AR transcripts, further explaining the potential AR upstream mechanism of ABCC5-mediated enzalutamide resistance, indicating that future development of specific ABCC5 inhibitors may be a promising strategy to target prostate cancer AR-antagonist resistance. This evidence concerns the gene AR and Familial prostate cancer.