Aims: Autosomal dominant polycystic kidney disease (ADPKD) is the most common mendelian disease in humans with an estimated prevalence of about one per 1000. The disease is caused by mutations in either one of two genes PKD1 or PKD2 (TRPP2). TRPP2 functions as a non-selective cation channel in the primary cilium. Activation of TRPP2 triggers cytosolic Ca2+ signals, but its physiological function in vivo remains unknown. The Drosophila melanogaster homologue of TRPP2 is a testis specific protein and is localised at the tip of the spermatozoan tail. TRPP2 is essential for male fertility. We used Drosophila melanogaster as a model organism to study TRPP2 function in vivo. Methods: The Drosophila melanogaster homologue of TRPP2 was knocked-out by homologous recombination and transgenic lines were generated using site-specific recombination. The phenotype of mutants was studied using multiple approaches including fertility tests, immunofluorescence and in-vivo confocal live imaging. Results: Absence or mislocalisation of the TRPP2 protein severely impaired fertility in Drosophila melanogaster. Male TRPP2 deficient flies are sterile although they produce motile, fully differentiated spermatozoan, which are effectively transferred to the female upon mating. Sterility is caused by a defect in directed movement of spermatozoan from the uterus to the female sperm storage organs. By using in-vivo confocal live imaging we studied the dynamics of directed spermatozoan movement in the female reproductive tract after mating to wild-type and TRPP2 mutant males. Conclusion: TRPP2 is required for directed spermatozoan movement in the female reproductive tract of Drosophila melanogaster. The real time analysis of TRPP2 mutant spermatozoan provides new insights into spermatozoan chemotaxis and TRPP2 signalling in vivo.