NOMO1 (NODAL modulator 1) is a transmembrane protein that functions as a component of the multi-pass translocon (MPT) complex, mediating insertion of multi-pass membrane proteins into the endoplasmic reticulum (ER) lipid bilayer 12. After SEC61 complex-mediated insertion of initial transmembrane segments, NOMO1 occludes the SEC61 lateral gate to facilitate subsequent transmembrane region insertion 2. Beyond translocon function, NOMO1 sustains ER structural integrity; NOMO1 depletion causes ER morphological collapse and autophagic responses 3. NOMO1 plays crucial roles in developmental biology and disease. It is essential for cardiomyocyte differentiation through Nodal signaling pathway activation 45. MicroRNA-33a-5p and the H19-encoded miR-675 post-transcriptionally regulate NOMO1 to control cardiomyocyte progenitor proliferation and trophoblast cell dynamics 56. Clinically, NOMO1 dysfunction is implicated in multiple pathologies. Rare loss-of-function variants associate with amyotrophic lateral sclerosis (ALS), with downregulated NOMO1 expression observed in ALS motor cortex layer 5 7. 16p13.11 micro-duplications encompassing NOMO1 predispose to congenital heart disease and laterality defects 8. Nomo1 deficiency in zebrafish causes autism-like behaviors with reduced brain melatonin; melatonin supplementation shows therapeutic potential 9. NOMO1 mutations represent prognostic markers in oral squamous cell carcinoma 10.