SYT15 (synaptotagmin 15) is a non-neuronal calcium-independent synaptotagmin family member involved in vesicle trafficking and exocytosis. Unlike classical synaptotagmins, SYT15 lacks Ca2+-dependent phospholipid binding activity in its C2 domains 1, though it retains type I membrane topology with a transmembrane domain. SYT15 is predominantly expressed in non-neuronal tissues including lung and testis 1. In lung adenocarcinoma, SYT15 functions as a tumor suppressor; reduced expression correlates with poor patient survival 2. SYT15 overexpression inhibits malignant phenotypes in lung cancer cells and suppresses the PI3K/AKT signaling pathway 2. Additionally, SYT15 expression influences immune cell infiltration in the tumor microenvironment and correlates with immunotherapy efficacy 2. Clinically, SYT15 emerges as a prognostic biomarker in platinum-resistant bladder cancer, where it was identified among genes predictive of chemotherapy response and overall survival 3. In paraquat-induced pulmonary fibrosis, SYT15 downregulation occurs during epithelial-mesenchymal transition 4. A congenic rat model identified SYT15 as carrying a potentially damaging polymorphism affecting metabolic syndrome components 5. These findings establish SYT15 as a multifunctional protein with implications for cancer prognosis and potential therapeutic targeting.