As inferred from homologs in mouse, PIWIL4 is loaded with piRNA in the cytosol and then translocates to the nucleus where it directs transcriptional silencing of cognate loci by an unknown mechanism. Most cellular PIWIL4 is translocated to the nucleus at E16.5 of mouse development and proper localization depends on PIWIL2 and TDRD1. TDRD9 and MAEL interact with PIWIL4, are observed in the nucleus, and may play a role in the translocation of PIWIL4. Knockout of TDRD9, however, does not affect nuclear localization of PIWIL4. Knockout of MAEL delays but does not prevent localization of PIWI4L to the nucleus. TDRKH is required for translocation of PIWIL4, however TDRKH is only observed in the cytosol.