Phospholipid scramblase involved in lipid homeostasis and membrane dynamics processes. Has phospholipid scramblase activity toward cholesterol and phosphatidylserine, as well as phosphatidylethanolamine and phosphatidylcholine. Required for autophagosome formation: participates in early stages of autophagosome biogenesis at the endoplasmic reticulum (ER) membrane by reequilibrating the leaflets of the ER as lipids are extracted by ATG2 (ATG2A or ATG2B) to mediate autophagosome assembly. Regulates ATP2A2 activity to control ER-isolation membrane contacts for autophagosome formation. In addition to autophagy, involved in other processes in which phospholipid scramblase activity is required. Modulates ER contacts with lipid droplets, mitochondria and endosomes. Plays an essential role in formation of cell junctions. Upon stress such as bacterial and viral infection, promotes formation of cytoplasmic vacuoles followed by cell death. Involved in the cytoplasmic vacuolization of acinar cells during the early stage of acute pancreatitis.; (Microbial infection) Host factor required for infection by all flaviviruses tested such as Zika virus and Yellow fever virus. Probably required post-entry of the virus to facilitate the ER membrane remodeling necessary to form replication organelles.