biostudies-literatureHanhsen Bthe European Union’s Horizon 2020 research and innovation programthe German Academic Exchange Service (DAAD)the Deutsche Forschungsgemeinschaft1666https://www.ebi.ac.uk/biostudies/studies/S-EPMC9139750biostudies-literatureUnknown11(10)CCCH zinc finger proteins (ZFPs) function mainly as RNA-binding proteins (RBPs) and play a central role in the mRNA metabolism. Over twenty seven CCCH-ZFPs are encoded in the genome of the human malaria parasite <i>Plasmodium falciparum</i>, the causative agent of malaria tropica. However, little is known about their functions. In this study, we characterize one member of the PfCCCH-ZFP named ZNF4. We show that ZNF4 is highly expressed in mature gametocytes, where it predominantly localizes to the cytoplasm. Targeted gene disruption of <i>ZNF4</i> showed no significant effect in asexual blood stage replication and gametocyte development while male gametocyte exflagellation was significantly impaired, leading to reduced malaria transmission in the mosquito. Comparative transcriptomics betweCellsThe <i>Plasmodium falciparum</i> CCCH Zinc Finger Protein ZNF4 Plays an Important Role in Gametocyte Exflagellation through the Regulation of Male Enriched Transcripts.PMC9139750NG170/1-1No 731060PR905/20-1Hanhsen BFarrukh ANgwa CJPradel GfalseThe <i>Plasmodium falciparum</i> CCCH Zinc Finger Protein ZNF4 Plays an Important Role in Gametocyte Exflagellation through the Regulation of Male Enriched Transcripts.CCCH zinc finger proteins (ZFPs) function mainly as RNA-binding proteins (RBPs) and play a central role in the mRNA metabolism. Over twenty seven CCCH-ZFPs are encoded in the genome of the human malaria parasite <i>Plasmodium falciparum</i>, the causative agent of malaria tropica. However, little is known about their functions. In this study, we characterize one member of the PfCCCH-ZFP named ZNF4. We show that ZNF4 is highly expressed in mature gametocytes, where it predominantly localizes to the cytoplasm. Targeted gene disruption of <i>ZNF4</i> showed no significant effect in asexual blood stage replication and gametocyte development while male gametocyte exflagellation was significantly impaired, leading to reduced malaria transmission in the mosquito. Comparative transcriptomics betwe2022-01-01T00:00:00Z2022 May2026-04-08T10:18:40.295Z2026-04-08T01:18:45.228ZS-EPMC91397503562670310.3390/cells11101666