TMEM49, now officially named VMP1, is a transmembrane protein localized mainly to the endoplasmic reticulum and autophagosome membranes. It is a key positive regulator of autophagy, interacting with Beclin-1 and supporting autophagosome formation, likely through phospholipid scramblase activity, and it also participates in selective autophagy such as zymophagy. Its disease roles are highly context-dependent: VMP1 is protective in acute pancreatitis and inflammatory bowel disease, but in certain cancers it can promote tumor progression, angiogenesis, or therapy resistance, while in others it may show tumor-suppressive effects. This functional heterogeneity makes VMP1 a complex and attractive research target.