Synaptophysin is the major integral membrane protein of small synaptic vesicles^1-3. It belongs to a family of proteins which includes synaptogyrin and synaptoporin. The protein contains 4 transmembrane domains and cytoplasmic N- and C-termini⁴. There are two intravesicular loops that contain disulfide bonds. The protein is N-glycosylated on the first intravesicular loop, a modification important for the synaptic vesicle targeting of synaptophysin. Indeed, a mutant form of the protein, unable to undergo glycolysation, leads to the accumulation of the protein in the cell body of neurons indicating that N-glycosylation is required for the synaptic localization of synaptophysin⁵. The C-terminal tail is extensively phosphorylated on Tyr residues. However, the biological significance of the post-translational modification is not yet determined⁶.

Although exact and specific role of synaptophysin remains a mystery, a study suggests that the protein is required for efficient endocytosis of synaptic vesicles in cultured hippocampal neurons⁶.

Since synaptophysin is exclusively detected in synaptic vesicles, it is widely used as a marker for presynaptic vesicles.

Genetic screening in humans and behavioral studies in rodents show that loss of synaptophysin expression or expression of a truncated form of the protein may be attributed to mental retardation and/or learning deficits^7,8. Interestingly though, synaptic transmission in synaptophysin knockout mice remains normal⁶.