Sig-1R normally resides at the ER, typically at the MAM, but when cells undergo stress (as expected following viral infection) the Sig-1R translocates to the peripheral ER network and plasma membrane to regulate a variety of cell surface proteins (Su et al., 2010), which might account for ligand-operated, Sig-1R-mediated modulation of virus attachment or entry (Figure 1). Here, SIGMAR1 is linked to viral infectious disease.