Abstract: Ixodes Scapularis salivary proteins, including Ixodes Scapularis anti-complement protein (Isac) and Isac-like protein family (ILP family) proteins, biologically functional equivalents and fragments thereof, and nucleic acid molecules encoding the same are disclosed. ILP family proteins, gene products and polypeptide fragments bind to proteins with thrombospondin repeats. Thus, therapeutic methods involving modulating proteins with thrombospondin repeats using ILP family proteins and biologically active polypeptide fragments thereof are also disclosed. ILP family proteins, gene products and polypeptide fragments have biological activity in modulating the complement pathway through specific binding to properdin. Thus, therapeutic methods involving modulating the complement pathway using ILP family proteins and biologically active polypeptide fragments thereof are also disclosed.