How flagellar signaling regulates the host interaction of parasites remains a challenge due to poor conservation of signaling systems with those in cilia of higher organisms. Flagellar cAMP signaling is implicated in interaction of the unicellular parasite Trypanosoma brucei with its hosts. The second messenger is produced by a large and atypical family of receptor-type adenylate cyclases (ACs) with unknown regulation mechanism. In order to identify trypanosome AC interacting proteins, ESAG4, an AC highly abundant in the parasite’s bloodstream stage, was fused to GFP and purified via GFP trap pull down followed by mass spectrometry.