Numerous studies using specific anti-CSP antibodies, monoclonal antibodies (mAbs), multiple mutations and/or inhibitors of protease cleavage, suggested that both N-and C-terminal domains bind to the hepatocyte surface heparan sulfate proteoglycans (HSPG) . Ordered hydrophobic cavities with unknown functions have been described on the crystallographic C-terminal domain that may be implicated in CSP-HSPG-binding. TSR residues 345 R and 347 L remain masked to Abs during circumsporozoite migration maintaining nonadhesive conformation. The N-terminal binding to HSPG induces proteolytic RI cleavage, unmasks TSR to an adhesive conformation and triggers hepatocyte invasion . Homologous TSR-like motifs are known in ~ 200 proteins from several species (~ 40 human), but the TSR of P.falciparum has unique disulphides .