VAMP8 is a SNARE protein essential for autophagosome-lysosome fusion, a critical step in autophagy. As a v-SNARE, VAMP8 localizes to lysosomal membranes and assembles with t-SNAREs (STX17 and SNAP29, or alternatively SNAP47) to form trans-SNARE complexes that drive membrane fusion 1. VAMP8 mediates both bulk autophagy during starvation and selective autophagy under nutrient-replete conditions 1. Beyond autophagy, VAMP8 functions in dense-granule secretion in platelets and participates in type I interferon antiviral responses 2. VAMP8 expression is regulated by post-translational acetylation and by transcriptional mechanisms involving the CREB-VAMP8 axis 34. Dysregulation of VAMP8 has disease implications: NRF2-controlled VAMP8 expression modulates ferroptosis sensitivity in ovarian cancer by controlling ferritin autophagy and labile iron pools 5, while CENPN-mediated VAMP8 suppression confers paclitaxel resistance in nasopharyngeal carcinoma 4. Genetic variants at the VAMP8 locus associate with periodontitis susceptibility and shared inflammatory pathways with atherosclerotic cardiovascular disease 6. Zinc-dependent inhibition of STX17-VAMP8 interaction can arrest oncogenic autophagy in multiple cancer types, representing a therapeutic strategy 7. These findings underscore VAMP8's pivotal role in lysosomal degradation pathways and emerging therapeutic potential.