Since gap junctions constituted by the Cx26 p.Gly45Arg variant are properly localized to the membrane and the variant is associated with hearing loss, we hypothesized that the permeability of Cx26 to second messengers like inositol trisphosphate (IP3) might be affected, as previously observed in studies of the Cx26 p.Val84Leu variant (Beltramello et al., 2005). The gene discussed is GJB2; the disease is hearing loss disorder.