VTI1B (Vesicle Transport through Interaction with t-SNAREs 1B) is a conserved Q-SNARE protein that mediates intracellular membrane trafficking by providing the Qb SNARE domain to four-helical SNARE bundles required for membrane fusion 1. VTI1B localizes primarily to endosomal compartments, the trans-Golgi network, and tubular structures, where it forms distinct SNARE complexes with syntaxin proteins and VAMP family members to regulate late endosome-to-lysosome fusion and autophagosome maturation 234. Mechanistically, VTI1B stability depends on its interaction partners; deletion of VTI1B leads to syntaxin 8 degradation while other SNARE partners compensate functionally 5. VTI1B participates in antimicrobial autophagy by mediating xenophagosome-lysosome fusion essential for degrading intracellular pathogens 3. Its function is regulated through phosphorylation by PTPN9; dephosphorylation promotes ATG16L1 precursor fusion and autophagosome biogenesis 4. Notably, mycobacterial trehalose dimycolate inhibits phagosome maturation by promoting aberrant VTI1B-VAMP2 complex formation instead of canonical VTI1B-VAMP8 complexes, facilitating intracellular pathogen survival 6. VTI1B dysregulation has been associated with Alzheimer's disease pathology based on altered plasma peptide profiles 7. VTI1B deficiency causes minimal phenotypes in most mice due to functional redundancy, though subtle autophagosomal accumulation occurs in hepatocytes 5.