Malaria is a global health problem that demands immediate practical actions to contain the high infection and mortality rates caused by Plasmodium species. Protective vaccine is still missing. Available drugs diminish their impact against Plasmodium as resistances are rising and expanding on the territories. While no vaccine of the current portfolio showed ideal protection and low-cost feasibility, drug development is still limited to formulation renewals or modifications of currently used drugs. Global health organizations committed to fight malaria identify the foremost reason of the stall on both vaccine development and drug discovery in the lack of knowledge about general mechanisms regulating the complex Plasmodium life cycle and the interactions with the host, especially with the immune system. Indeed, despite in the past few decades Plasmodium research was notably forwarded by availability of new tools, genome, microarray and proteomic data, basic and important questions on its biology are still shockingly unanswered. The field is still in great demand of approaches that allow discovering the function of ~2/3 of the genome encoded proteins. In order to respond to this need, I developed in Plasmodium falciparum a novel molecular tool for random mutagenesis that permits large scale mutant productions. This is expected to produce sortable mutants at an unprecedented frequency of 1 in 10^2 parasites by induction of a constitutively latent stable transposase. This tool is ideal to identify gene function and essentiality. By using it, we propose to investigate and characterize proteins and mechanisms i) involved in immune system-pathogen interactions; ii) critical for asexual growth and iii) essential for sexual differentiation. Our results will contribute significantly to the discovery of new targets to block Plasmodium asexual and transmission forms, and for the first time to systematically identify parasite virulence factors influencing host immune responses.