Although the molecular basis of CDI remains unclear, recent studies have suggested that CDI involves functional coupling of the inactivation domain (ID) of STIM1 (Derler et al., 2009; Scrimgeour et al., 2009; Mullins and Lewis, 2016a) with the inner pore residues 76–91 of Orai1 (Mullins et al., 2016b). This evidence concerns the gene STIM1 and clostridium difficile infection.