SEC31B is a mammalian orthologue of yeast Sec31p and a structural component of the COPII vesicle coat complex, which mediates cargo export from the endoplasmic reticulum (ER) 1. As part of COPII, SEC31B functions in ER-to-Golgi vesicular trafficking and cargo loading 2. The protein exists in two main forms: SEC31B-F (full-length, ~129 kDa) containing WD repeats that bind Sec13 and a proline-rich C-terminus that binds Sec23/24, and SEC31B-T (truncated, ~53 kDa) with preserved WD-repeat domain but lacking the C-terminal region 1. SEC31B localizes to the ER, vesicular-tubular clusters, and COPII-coated vesicles, where it may coordinate with calcium signaling through interaction with ALG-2 protein 3. The gene undergoes extensive alternative splicing, with only 16 of 29 exons constitutively utilized 1. Clinically, SEC31B variants associate with resting heart rate variation in humans, with a non-synonymous variant significantly linked to SEC31B expression in heart and nerve tissues 4. SEC31B expression levels correlate with glioma prognosis and treatment responsiveness, with lower expression associated with better survival outcomes and improved chemotherapy response 5. Additionally, SEC31B has been identified as a hub gene in prostate cancer-related fatigue pathways, enriched in CXCL signaling 6, and identified as a splicing factor associated with glioblastoma patient survival 7.