NTCP is functionally conserved in mammalians, but protein sequences of NTCP vary among species, which is likely to contribute to the narrow species tropism of viral infection. Strikingly, despite the high level of protein sequence homology between human and monkey NTCP, the later did not support HBV and HDV infection. Replacing a small motif of aa 157-165 of mkNTCP with the corresponding hNTCP residues converted mkNTCP to a receptor for pre-S1 binding as well as HDV and HBV infection. Further studies are warranted to determine if and how NTCP contributes to the species specificity of HDV and HBV infection in other species. It also remains to be determined if other molecule(s) additional to NTCP contributes to the cellular entry of HBV and/or HDV as a coreceptor(s) or receptor component(s), and if other host factors such as the microenvironment or architecture of hepatocytes in liver, or soluble blood components like those that have been shown to involve in infections of other viruses (Shayakhmetov et al., 2005; Morizono et al., 2011) , contribute to HBV and/or HDV infection.