After elucidating the effect of NOMO1 loss in the NOMO1–NCLN–TMEM147 complex, we evaluated its role in activating the Nodal signaling pathway, essential for cellular differentiation during embryonic development [20] and reactivation in multiple tumor types [21], where it has been related to increased proliferation and invasion [18,54]. Here, TMEM147 is linked to neoplasm.