TMEM167A is a transmembrane protein involved in endoplasmic reticulum (ER) to Golgi trafficking within the early secretory pathway 1. It functions as part of a protein complex that regulates vesicular transport and endosomal system dynamics 2. The protein is highly expressed in pancreatic β cells and neurons 1, tissues critical for glucose homeostasis and neurological function. Biallelic TMEM167A variants cause Microcephaly, Epilepsy, and Diabetes Syndrome (MEDS), a severe neonatal disorder presenting with diabetes diagnosed before 6 months of age, severe microcephaly, and epilepsy in most patients 1. Mechanistically, TMEM167A variants impair proinsulin trafficking to the Golgi and sensitize β cells to ER stress, leading to β cell dysfunction 1. The protein also regulates unfolded protein response activation in B cells and forms a complex with IER3IP1 3. Beyond monogenic disease, TMEM167A variants show associations with common metabolic traits, including lipid levels in genome-wide interaction analyses 4, and have been identified as potential biomarkers in pulmonary tuberculosis diagnosis 5. Additionally, TMEM167A polymorphisms associate with antipsychotic-induced involuntary movements 6, suggesting broader roles in neurological function. These findings highlight TMEM167A's critical importance in secretory pathway function and cellular stress responses across multiple tissues.