CCDC47 (coiled-coil domain containing 47) is an endoplasmic reticulum (ER) transmembrane protein with critical roles in membrane protein biogenesis and calcium homeostasis. As a component of the multi-pass translocon (MPT) complex, CCDC47 functions within the PAT (protein associated with ER translocon) subcomplex to mediate insertion of multi-pass membrane proteins into the lipid bilayer 1. Specifically, CCDC47 occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions after initial protein segments are inserted 1. Beyond membrane protein biogenesis, CCDC47 regulates ER calcium ion homeostasis through its calcium-binding acidic luminal domain and interacts with store-operated calcium entry mediators including STIM1 and Orai1 23. CCDC47 also participates in ER-associated degradation (ERAD) pathways and is essential for ER organization during embryogenesis 4. Clinically, bi-allelic loss-of-function variants in CCDC47 cause trichohepatoneurodevelopmental syndrome (THNS), characterized by global developmental delay, dysmorphic features, woolly hair, liver dysfunction, hypotonia, and elevated bile acids 25. Cellular studies from affected individuals demonstrate decreased ER calcium storage, impaired IP3R-mediated calcium signaling, and reduced store-operated calcium entry 2. Additionally, a CCDC47-PRKCA gene fusion has been identified in adult choroid plexus papilloma with aggressive clinical behavior 6.