Synaptophysin (SYP) is a transmembrane glycoprotein localized to synaptic vesicles and neuroendocrine microvesicles 1 that regulates neurotransmitter release and synaptic plasticity 2. SYP functions in synaptic vesicle organization and targeting, and regulates both short-term and long-term synaptic plasticity through mechanisms involving protein binding and cholesterol interactions. At the molecular level, SYP serves as a structural organizer of membrane components and facilitates vesicle trafficking to the presynaptic membrane 1. Disease relevance is significant: SYP mutations cause X-linked intellectual developmental disorder 96, identified through systematic X-chromosome X screens 3. Additionally, SYP is upregulated as a neuroendocrine differentiation marker in aggressive prostate cancer progression, particularly in castration-resistant and neuroendocrine prostate cancer where MUC1-C activation drives SYP expression 45. Genetic polymorphisms in SYP (rs2293945 and rs3817678) associate with attention-deficit/hyperactivity disorder susceptibility in Korean children, particularly in females 2. Furthermore, SYP puncta within microglia serve as synaptic engulfment markers after stroke, with STING inhibition reducing microglial phagocytosis of SYP-positive synapses and improving motor recovery 6. These findings establish SYP as both a critical synaptic function protein and a biomarker for neurological and neuroendocrine diseases.