Anopheles sp. mosquitoes expresses hundreds of sequence-specific ORs with only ~ 20 % amino acid identities among them, in contrast to their ORCO partners that are nearly invariant, most probably to preserve functionality across the ORCO+OR modular assemblies. Although the molecular stoichiometry and mechanisms of each ORCO+OR complexes to transduce volatile-binding into ion flow to activate OR odor detection are not yet known, ORCO -/-mutants 4 cannot correctly assemble or function . In contrast, in the absence of ORs (like it occurs in primitive insects or may be observed in vitro), ORCO forms tetrameric ionconducting channels that can be monomerically activated by molecular agonists (i.e., VUAA1). In vitro isolated ORCO forms homotetramers of heptahelical protein monomers , mostly embedded into the mosquito olfatory neuronal cell membrane. The tetramers surround an ion-conducing pore formed by their central α-helices (Graphical Abstract, yellow α-helices). Each monomer forms a chemica volatil-detecting cavity (Graphical Abstract, green α-helices) that allosterically affects ion conductance.