Vapa, also known as VAMP-associated protein A, is an endoplasmic reticulum-resident membrane protein involved in multiple biological functions. It plays key roles in inter-organellar lipid transport, which is crucial for maintaining cellular lipid homeostasis and normal cell function. It is associated with pathways related to autophagy, cell motility, and immune responses [2,4,5].

In hepatocellular carcinoma, large oncosomes-loaded Vapa promotes bone-tropic metastasis by forming an osteoclastic pre-metastatic niche. Vapa-enriched large oncosomes induce pre-metastatic education in the bone, transforming it into a favorable environment for metastatic HCC cell growth. Mechanically, Vapa delivered by large oncosomes activates N-WASP in osteoclasts, leading to actin cytoskeleton reorganization and osteoclastogenesis [1]. In macrophages infected with Leishmania amazonensis, knockdown of Vapa prevents the replication of the parasite and impairs parasitophorous vacuole expansion, as Vapa is required for lipid transport between the parasitophorous vacuoles and the host cell endoplasmic reticulum [3].

In conclusion, Vapa is essential for processes such as lipid transport, metastasis in cancer, and parasite replication in host cells. These findings from functional studies provide insights into its role in disease conditions, highlighting its potential as a therapeutic target in areas like cancer metastasis prevention and treatment of Leishmania-related infections.