The present disclosure relates to blood brain barrier shuttles comprising a brain effector entity, a linker and one monovalent binding entity that bind to a transferrin receptor, wherein the linker couples the effector entity to the monovalent binding entity which binds to the transferrin receptor, wherein the monovalent binding entity which binds to the blood brain barrier receptor comprises one scFab directed to the transferrin receptor recognizing an epitope in the transferrin receptor comprised within the amino acid sequence of Seq. Id. No. 14, 15 or 16.
