The Plasmodium parasite undergoes sexual reproduction once during a life cycle, and this occurs in the mosquito (Figure 1). Its genome is haploid, except briefly after fertilization. The factors that initiate and regulate the formation of gametocytes are not yet well understood (67). Ingestion of gametocytes by a mosquito during a blood meal activates the formation of gametes (gametogenesis) in the mosquito midgut lumen. A mosquito-derived molecule, xanthurenic acid, in addition to temperature shift and pH change, can trigger male gametogenesis in the form of exflagellation (14, 15). P48/45 is a male-gamete-specific surface protein belonging to the 6-cysteine repeat protein family. Using a genetic deletion analysis study, van Dijk et al. (144) showed that P48/45 is essential for the male gamete’s ability to fertilize a female gamete in P. berghei. A paralog of P48/45, named P47, is exclusively expressed on the surface of female gametes. However, in contrast to P48/45, genetic deletion of P47 did not have any impact on female gamete fertilization by a male gamete (146). Another member of the 6-cysteine repeat protein family is P230, which is expressed on the surface of male and female gametes and is recognized as a candidate for malaria transmission blocking strategies (33). Knockout studies of P230 in P. falciparum revealed an important but unidentified function during gamete fertilization in the mosquito midgut (32).