BET1 encodes a Golgi vesicular membrane trafficking protein essential for secretory pathway function. As a SNARE protein, BET1 is required for vesicular transport from the endoplasmic reticulum (ER) to the Golgi complex, specifically mediating fusion of ER-derived vesicles with the ER-Golgi intermediate compartment (ERGIC) and cis-Golgi membrane 1. BET1 functions as part of a SNARE complex with GOSR2, SEC22b, and syntaxin-5 to accomplish this essential membrane fusion step 1. Beyond canonical ER-Golgi transport, BET1 interacts with additional factors including ERGIC-53, and can be recruited to alternative trafficking pathways, such as those involving MT1-MMP transport to invadopodia in invasive cancer cells 2. Biallelic BET1 variants cause severe congenital muscular dystrophy (CMD) with epilepsy, establishing impaired vesicular transport as a pathogenic mechanism 1. Disease-associated variants reduce BET1 protein levels through aberrant splicing or disrupt protein interactions, compromising ERGIC-53 binding and causing protein mislocalization 1. The clinical significance of BET1 is further underscored by its role in regulating the secretory pathway under metabolic stress, as BET1-containing SNARE complexes are subject to negative regulation by the lactate and hypoxia sensor NDRG3 3. These findings establish BET1 as a critical component of the secretory pathway with direct relevance to inherited neuromuscular disease.