RABGAP1L, a Tre2/Bub2/Cdc16 (TBC) domain-containing protein involved in the regulation of small membrane-bound GTPases, was identified in an RNAi screen to robustly potentiate the antiviral action of Interferon (IFN) against influenza A viruses (IAVs). Functional studies revealed that the catalytically active TBC domain of RABGAP1L promotes antiviral activity. By using proximity-labeling approaches, the aim was to investigate the protein’s interactome and thereby identify its possible role in existing signaling pathways.