TMEM131 is a conserved transmembrane protein that functions as a collagen binding factor essential for extracellular matrix protein secretion. Structurally, TMEM131 contains PapD chaperone-like domains at its amino terminus that recruit and facilitate proper assembly of premature collagen monomers in the endoplasmic reticulum (ER) 1. Its carboxy terminus interacts with TRAPPC8, a component of the TRAPP tethering complex, to mediate collagen cargo trafficking from the ER to the Golgi apparatus 1. TMEM131 cooperates with TMEM39A to facilitate bulk transport of extracellular matrix proteins through formation of large COPII vesicles, a process conserved across metazoans and essential for rapid secretion of structural components 2. Beyond collagen regulation, TMEM131 mediates secretory trafficking of other cargo including soluble TRAIL through COPII-dependent transport, where it interacts with TRAIL at the ER and routes it to the Golgi via Sec23 homolog A 3. TMEM131 also functions as an ER-phagy regulator, controlling selective autophagy of ER during aging 4. Disease associations include altered methylation patterns in Down syndrome 5, and potential involvement in idiopathic pulmonary hypertension with metabolic syndrome 6. These functions establish TMEM131 as a critical coordinator of secretory trafficking and cellular adaptation processes.