The involvement of the extracellular GAPDH of S. pyogenes in C5a sequestration (Terao et al., 2006) and of the S. pneumoniae enzyme in C1q binding (Terrasse et al., 2012) provide reference cases for the existence of complement immunoevasion mechanisms in streptococcal infections that depend on the moonlighting action of GAPDH. This evidence concerns the gene C5 and streptococcal infection.