GOSR2 encodes Membrin, a cis-Golgi SNARE protein essential for intra-Golgi vesicle transport and ER-to-Golgi protein trafficking 1. The protein functions as a t-SNARE that mediates fusion between COPII vesicles budding from the endoplasmic reticulum and the cis-Golgi membrane, enabling cargo delivery through the secretory pathway 1. Pathogenic biallelic GOSR2 mutations cause primarily neurological disease through loss of function, preventing proper GOSR2 localization to the cis-Golgi 2. The expanded phenotypic spectrum includes progressive myoclonus epilepsy (PME), progressive myoclonus ataxia (PMA), congenital muscular dystrophy, and hearing loss 3. The original homozygous founder mutation (c.430G>T; p.Gly144Trp) causes North Sea-PME with early-onset ataxia, areflexia, action myoclonus, and seizures 2. Emerging evidence demonstrates that GOSR2 mutations associate with hypoglycosylation of α-dystroglycan in muscular dystrophy, linking membrane trafficking dysfunction to dystroglycanopathy 4. Phenotypic severity correlates with specific isoform involvement and mutation type 3. Additionally, genome-wide association studies identified GOSR2 variants associated with anomalies of thoracic arteries and veins during cardiac development 5 and with blood pressure regulation 6, suggesting roles beyond neurological disease.