NCLN (nicalin) is a membrane protein that functions primarily as a component of the multi-pass translocon (MPT) complex, mediating the insertion of multi-pass membrane proteins into cellular membranes 12. The MPT complex works in conjunction with the SEC61 complex, taking over protein insertion after SEC61 inserts the initial transmembrane segments by occluding the lateral gate to facilitate insertion of subsequent transmembrane regions 2. Beyond its role in protein trafficking, NCLN forms a membrane protein complex with NOMO (Nodal modulator) that regulates axial mesendoderm patterning during embryonic development through modulation of Nodal signaling pathways 3. Functional studies in zebrafish embryos demonstrate that NCLN is essential for enteric nervous system development, with knockdown experiments showing disrupted ENS formation 4. Additionally, NCLN has been implicated in various pathological contexts, including differential expression in Ebola survivors with optic neuropathy 5, association with oral squamous cell carcinoma 6, and potential involvement in skin pigmentation traits through genetic variants 7. The protein's diverse roles span from fundamental cellular processes like membrane protein insertion to complex developmental signaling and disease pathogenesis.