SYT4 (synaptotagmin 4) is a calcium-sensing vesicle protein with dual roles in neuronal function and cancer pathogenesis. In normal physiology, SYT4 does not directly bind Ca2+ but regulates neuronal dense core vesicle (DCV) trafficking through interaction with motor protein KIF1A; MAPK8/JNK1-mediated phosphorylation destabilizes this interaction to capture DCVs at synapses 1. SYT4 is abundant in cerebellar GABAergic neurons during development and adulthood 2. During pancreatic β cell maturation, SYT4 expression increases ~8-fold and inversely regulates readily releasable insulin granule pools, modulating glucose-stimulated insulin secretion sensitivity 3. In pathological contexts, SYT4 emerges as a pro-oncogenic driver across multiple cancer types. In gastric cancer, SYT4 is upregulated and promotes proliferation, cell cycle progression, and apoptosis suppression via two distinct mechanisms: direct interaction with PSMC6 to activate Wnt/β-catenin signaling 4, and enhancement of intracellular Ca2+ influx through MAPK pathway activation 5. The calcium channel blocker amlodipine suppresses SYT4-driven gastric cancer growth 5. In prostate cancer, SYT4 binds SNAP25 to promote exosomal secretion, conferring enzalutamide resistance 6. Neuropsychiatrically, SYT4 overexpression in the medial prefrontal cortex drives chr18 stress-induced anhedonia via BDNF-TrkB signaling suppression 7, and SYT4 is identified as a bipolar disorder-associated gene 8.