SEC31A is an outer coat protein of the COPII (coat protein complex II) complex, which mediates transport of newly synthesized proteins from the endoplasmic reticulum (ER) to the Golgi apparatus. The protein functions in cargo selection and physical deformation of ER membranes to form transport vesicles. Beyond classical secretory trafficking, SEC31A participates in specialized membrane transport processes: it interacts with ATG9a to regulate autophagosome formation during osteogenic differentiation of mesenchymal stem cells 1, and it associates with the adapter protein Nlp to maintain specificity during COPII and COPI-coated vesicle transitions 2. SEC31A expression is regulated by alternative splicing in a tissue-specific manner via RBM47, with increased exon inclusion in digestive tissues correlating with enhanced lipid transport 3. Homozygous loss-of-function mutations in SEC31A cause Halperin-Birk syndrome, a severe neurodevelopmental disorder characterized by profound developmental delay, brain malformations, spastic quadriplegia, seizures, and early lethality, with pathogenesis mediated through ER-stress pathway activation 4 5. SEC31A also serves as a fusion partner in oncogenic translocations: SEC31A-JAK2 fusions occur in classical Hodgkin lymphoma and ALK-positive large B-cell lymphoma, and respond to JAK inhibitors 6 7. In pancreatic cancer, cancer-associated fibroblast-derived circRNAs stabilize SEC31A protein to enhance CXCL12 secretion, promoting perineural invasion 8.