Binary actin-ADP-ribosylating toxins (e.g., Clostridium botulinum C2 toxin or Clostridium perfringens iota toxin ) consist of two separate proteins: An ADP-ribosyltransferase, which modifies actin thereby inhibiting actin polymerization, and a binding component that forms heptamers after proteolytic activation. While C2 toxin interacts with carbohydrate structures on host cells, the group of iota-like toxins binds to lipolysis-stimulated lipoprotein receptor (LSR). Here, we review LSR and discuss the role and function of LSR in interaction of iota-like toxins with host cells.