Vesicle-associated membrane protein-associated protein A (VAPA)

Vesicle-associated membrane protein-associated protein A (VAPA) is an **integral type II membrane protein** that primarily localizes to the endoplasmic reticulum and related organelles[1][3][4][9]. It acts as a dynamic tether at multiple membrane contact sites, facilitating the exchange of lipids and contributing to organelle membrane tethering, lipid transfer, and membrane trafficking[2][3][4][9][10]. VAPA exerts its functions through direct interactions with proteins containing the FFAT motif, such as oxysterol-binding protein, glycolipid transfer protein, and ceramide transfer protein, coordinating the nonvesicular transport of bioactive lipids like ceramide and cholesterol between the ER and other organelles[2][5][8][11]. VAPA also binds a variety of SNARE proteins and proteins associated with vesicle trafficking, suggesting a role in membrane fusion and vesicle transport[1][3]. It is hijacked by several RNA viruses (e.g., hepatitis C virus, norovirus) to facilitate viral genome replication and assembly, highlighting its importance as a host factor in infection[1][2][3]. Although VAPA itself is not generally viewed as a direct therapeutic target, its partner VAPB is implicated in neurodegenerative disorders such as ALS8, with functional redundancy between VAPA and VAPB suggested[5][4]. No approved drugs or drug mechanisms are known to act directly on VAPA. VAPA has no established role as a biomarker nor are notable safety concerns or therapeutic challenges described in the literature. It is essential to multiple cellular processes, and its loss or dysfunction could impact organelle communication, lipid homeostasis, and possibly contribute to neurodegeneration and susceptibility to viral infection[3][4][5][10][11].

Other names

VAP-AVAP33VAMP-A33 kDa VAMP-associated proteinhVAP-33VAP-33epididymis secretory sperm binding proteinvesicle-associated membrane protein-associated protein AVAMP (vesicle-associated membrane protein)-associated protein A