{Reference Type}: Journal Article {Title}: Melatonin as a Circadian Marker for Plasmodium Rhythms. {Author}: Dias BKM;Mohanty A;Garcia CRS; {Journal}: Int J Mol Sci {Volume}: 25 {Issue}: 14 {Year}: 2024 Jul 17 {Factor}: 6.208 {DOI}: 10.3390/ijms25147815 {Abstract}: Plasmodium, a digenetic parasite, requires a host and a vector for its life cycle completion. Most Plasmodium species display circadian rhythmicity during their intraerythrocytic cycle within the host, aiding in immune evasion. This rhythmicity, however, diminishes in in vitro cultures, highlighting the importance of host-derived signals for synchronizing the parasite's asexual cycle. Studies indicate a species-specific internal clock in Plasmodium, dependent on these host signals. Melatonin, a hormone the pineal gland produces under circadian regulation, impacts various physiological functions and is extensively reviewed as the primary circadian marker affecting parasite rhythms. Research suggests that melatonin facilitates synchronization through the PLC-IP3 signaling pathway, activating phospholipase C, which triggers intracellular calcium release and gene expression modulation. This evidence strongly supports the role of melatonin as a key circadian marker for parasite synchronization, presenting new possibilities for targeting the melatonin pathway when developing novel therapeutic approaches.