Vesicle-associated membrane protein-associated protein B (VAPB)

Vesicle-associated membrane protein-associated protein B (VAPB) is a type IV, tail-anchored membrane protein predominantly localized to the endoplasmic reticulum (ER), where it is essential for forming membrane contact sites with other organelles, mediating lipid transfer, regulating calcium homeostasis, autophagy, and the unfolded protein response[1][3][5][6]. VAPB functions as a tether and scaffolding protein, interacting with proteins containing FFAT (two phenylalanines in an acidic tract) motifs via its major sperm protein (MSP) domain, and recruits multiple partners to the ER surface[3][5]. Mutations in VAPB, most notably the P56S variant, are causative for amyotrophic lateral sclerosis type 8 (ALS8) and associated with other motor neuron diseases; these mutations alter VAPB structure or aggregation, leading to cellular dysfunction and neurodegeneration[2][3][4][6]. VAPB is part of the VAPA/B protein family, with VAPA sharing strong similarity and overlapping function; VAPB may form homodimers or heterodimers with VAPA for diverse cellular roles[3][5][6]. While essential for neuronal health, no direct pharmacological modulators of VAPB exist; current research focuses on understanding its biology and mechanisms underlying disease.

Other names

Vesicle-associated membrane protein-associated protein CVAP-BVAP-CALS8VAMP (vesicle-associated membrane protein)-associated protein B and CVAMP-associated protein B/CVAMP-associated 33 kDa proteinVAMP-B/VAMP-CUNQ484/PRO983

None established—no drugs target VAPB directly, but disease mechanism involves loss of function, protein aggregation, and loss of interaction affecting cellular homeostasis[2][3][4][6]