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Once ingested, they are then activated into gametes to continue the parasite life cycle in the mosquito midgut. Both persistence of gametocytes in the blood and their activation into gametes are tightly regulated by phospho-signaling. While the serine-threonine phosphatase\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PP1 is an essential enzyme for asexual blood stage parasite proliferation, its role during transmission of sexual stages remains elusive. Here, we employed a conditional depletion strategy to conduct a functional analysis of\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PP1 during gametocyte development, gamete formation, and transmission to mosquitoes. We show that\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PP1 regulates the deformability and the permeability of mature gametocyte-infected erythrocytes through the dephosphorylation of protein kinase A (PKA) substrates, thus highlighting a key role for\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PP1 in modulating the host cell mechanical properties, which are crucial for gametocyte persistence in the bloodstream. We also provide evidence that\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PP1 controls crucial steps of gametocyte activation via stimulation of the cyclic GMP (cGMP)\/protein kinase G (PKG) pathway. Collectively, these results underscore the pivotal role of\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PP1 in the transmission of\n                      <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                      to the mosquito during both gametocyte development and gamete formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The protein phosphatase PP1 is a major contributor to total cellular phosphatase activity in eukaryotes and plays a critical role during various cellular processes. Here, we have unraveled novel mechanisms regulated by the phosphatase\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PP1 in the human malaria parasite\n                      <jats:italic toggle=\"yes\">Plasmodium falciparum<\/jats:italic>\n                      . While\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PP1 is known to be essential for the parasite\u2019s asexual proliferation, in the present study, we demonstrate that\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PP1 is also required during the sexual parasite stages, called gametocytes, that ensure parasite transmission from humans to mosquitoes.\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PP1 regulates the mechanical properties of the gametocyte-infected host cell, a process necessary for gametocyte persistence in blood circulation. Moreover,\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PP1 also contributes to the activation of gametocytes into gametes, the stages that pursue the parasite life cycle in mosquitoes. In addition to providing insights into novel mechanisms involved in parasite transmission, this study also highlights the possibility of interfering with the\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PP1 signaling pathway for blocking malarial parasite transmission.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00874-25","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T12:00:27Z","timestamp":1755518427000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>Plasmodium falciparum<\/i>\n                    PP1 phosphatase is a key regulator of malaria parasite 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