VAMP3, also known as vesicle-associated membrane protein 3 or cellubrevin, is a vesicular-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) [2,6]. It is involved in exocytic and endocytic pathways, driving the fusion of secretory granules with the membrane in mast cells [2]. In addition, it plays a role in processes such as membrane fusion, protein secretion, and the regulation of vesicle trafficking, which are crucial for normal cellular function [4].

In myeloid cell-specific Vamp3 knockout (Vamp3 Δmyel) mice, a reduction in TNF-α and IL-6 release from macrophages was observed, along with decreased paw edema, ankle joint swelling, mechanical allodynia, and thermal hyperalgesia induced by complete Freund's adjuvant (CFA) [3]. This indicates that Vamp3 is involved in regulating inflammatory responses and pain.

In human neuroblastoma cells, reduced VAMP3 stimulated cell proliferation and suppressed apoptosis, while increased VAMP3 had the opposite effects, suggesting its role in tumor-related cell behavior [1].

In astrocytes, down-regulation of Vamp3 expression disrupted endocytic BDNF secretion without affecting uptake or transport, showing its function in BDNF recycling [5].

In conclusion, VAMP3 is essential for various cellular processes including vesicle-mediated secretion, regulation of inflammation, and cell survival. Studies using gene-knockout mouse models have revealed its significant contributions to inflammatory diseases, such as those involving macrophage-mediated inflammation, and to tumor-related cell behavior in neuroblastoma. These findings highlight VAMP3 as a potential therapeutic target for these disease areas.