To date, several target proteins of RNF4 have been identified, including Mediator of DNA damage checkpoint 1 (MDC1), breast cancer susceptibility gene I (BRCA1), and progressive multifocal leukoencephalopathy (PML), many of which are involved in DNA repair, nucleic acid metabolism, and chromatin regulation. Here, MDC1 is linked to progressive multifocal leukoencephalopathy.