SYT5 (synaptotagmin 5) is a calcium sensor protein located on chromosome 19.4 that regulates Ca2+-dependent exocytosis across multiple cellular compartments. Primary function: SYT5 functions as a Ca2+ and phospholipid sensor that coordinates vesicle fusion events through C2 domain-mediated binding 1. Mechanism: SYT5 decodes Ca2+ signals released by intracellular channels to trigger membrane fusion. In autophagy, SYT5 binds both Ca2+ and phosphatidylinositol-4-phosphate (PtdIns4P) to form a fusion complex essential for autophagosome-lysosome fusion 1. SYT5 similarly regulates Weibel-Palade body exocytosis in endothelial cells, where Ca2+ binding to its C2 domain is critical for von Willebrand factor secretion 2. Disease relevance: SYT5 expression correlates with pancreatic β-cell function; tacrolimus reduces SYT5 expression and impairs insulin secretion in human islets 3. Autoantibodies against SYT5 are associated with relapse in ANCA-associated vasculitis 4, and anti-bacterial antibodies cross-reactive with SYT5 may impair neuronal vesicle recycling 5. Clinical significance: SYT5 represents a target for understanding drug-induced diabetes and potential immunological complications in vasculitis management.