SYT8 (synaptotagmin 8) is a calcium-regulated exocytotic protein expressed in non-neural tissues that mediates vesicular trafficking and secretion. Unlike neural synaptotagmins, SYT8 lacks calcium-dependent phospholipid binding but retains SNARE and clathrin-AP2 interaction domains 1, positioning it as a general vesicle trafficking regulator rather than a calcium sensor. In pancreatic β-cells, SYT8 plays a non-redundant role in insulin secretion through long-range chr11 interactions with the INS promoter located ~300 kb away 2. Glucose stimulation increases INS-SYT8 physical contact and SYT8 expression, and SYT8 knockdown significantly reduces insulin secretion 32. SYT8 is additionally involved in sperm acrosomal reactions and may regulate exocytosis in other hormone-secreting cells. Clinically, SYT8 serves as a specific biomarker for gastric cancer peritoneal metastasis, with elevated expression independently predicting peritoneal recurrence-free survival in stage II/III patients 4. SYT8 expression correlates with increased invasion, migration, and chemotherapy resistance; SYT8 knockdown decreases these phenotypes and improves therapeutic outcomes in xenograft models 4. SYT8 also appears in a dual-marker prognostic panel with MAGED2 for gastric cancer risk stratification 5. Additionally, SYT8/TNNI2 fusion transcripts occur in 37.5% of bladder cancer specimens 6, and SYT8 was identified in genomic instability signatures predicting NSCLC prognosis 7.