Selenoprotien W (SelW) plays a key role in brain development, although the exact biological function and mechanisms remain unclear. We performed a yeast two-hybrid screen on a human fetal brain cDNA library and identified FAM96B as a novel binding partner of SelW. FRET analyses confirmed the interaction between SeIW' and FAM96B. The mutated SeIW' construct was cloned and overexpressed in E. coli, and a pull-down assay verified a direct interaction between SeIW' and FAM96B. Finally, Co-Immunoprecipitation on murine brain tissue proteins demonstrated an endogenous interaction between the two proteins in the brain. Taken together, our findings prove a direct interaction between SelW and FAM96B, which may provide new insights into the role of SelW in brain development and neurodegenerative diseases. (C) 2019 Elsevier Inc. All rights reserved.