Importantly, our results revealed the essential function of TbCDC34 for the replication of T. brucei. Effective clearing from infection observed upon knockdown of TbCDC34, the activity inhibition with the small molecule CC0651 (Fig 8) and structural differences between the human and trypanosomal CDC34 which should facilitate development toward specificity, indicate that TbCDC34 could be considered as a potential novel drug target in the African sleeping sickness. Here, CDC34 is linked to human African trypanosomiasis.