SEC24D is a cargo-selective component of the COPII coat complex that mediates transport of newly-synthesized proteins from the endoplasmic reticulum (ER) to the Golgi apparatus 1. As part of COPII, SEC24D promotes physical deformation of ER membranes and selects cargo molecules for vesicular transport 234. SEC24D has specialized cargo specificity compared to other SEC24 isoforms, particularly packaging GPI-anchored proteins via TMED10 and IxM motif-containing SNAREs 34. Functionally, SEC24D is dynamically regulated by O-GlcNAcylation during collagen transport, which modulates COPII interactions including with myoferlin to facilitate ER exit site fusion 5. SEC24D mutations cause Cole-Carpenter syndrome 2, a rare autosomal recessive osteogenesis imperfecta 6. SEC24D deficiency induces osteogenic differentiation deficiency through ER stress and inactivation of the ATF6/TGF-β/Runx2 regulatory loop 6. Beyond skeletal disease, SEC24D represents a susceptibility gene for hepatitis B virus infection, with protective effects observed in non-infected liver tissues 7. In cancer, SEC24D overexpression correlates with metastatic progression in renal, lung, and gastric cancers and associates with increased CD8+ T cell infiltration 1. Acquired SEC24D mutations in melanoma impair STING trafficking, reducing type I interferon production and contributing to immunotherapy resistance 8.