Most secretory proteins, membrane proteins, and lipids are synthesized in the ER and packaged into coat protein complex II (COPII) as they exit endoplasmic reticulum exit site (ERES) for trafficking to ER-Golgi intermediate compartment (ERGIC), Golgi, and other organelles. This process is essential for the maintenance of cellular functions. In addition to the basic components of COPII, SAR1, SEC23/SEC24, SEC13/SEC31, more proteins were found to participate in the ER to Golgi vesicle transport, including cTAGE5/MEA6 (cutaneous T cell lymphoma-associated antigen 5C/ meningioma-expressed antigen 6) (Ma and Goldberg, 2016). Recent studies of cTAGE5/MEA6 are focused on its relationship with the COPII complex and its biological functions (Wang et al., 2016; Fan et al., 2017; Zhang et al., 2018). Here, we will briefly review the physiological functions of cTAGE5/MEA6 and underlying mechanisms.