Complexin-2

Complexin-2 (CPLX2) is a 134-amino acid presynaptic protein that regulates synaptic vesicle exocytosis through dual roles: it negatively regulates vesicle clustering at the active zone while positively regulating late-stage exocytosis of synaptic and secretory vesicles (UniProt: Q6PUV4). The protein is also implicated in mast cell degranulation, indicating broader roles in calcium-dependent exocytosis.

CPLX2 is predominantly expressed in neurons, where it fine-tunes the balance between vesicle mobilization and release at the synapse. No primary disease associations are documented in UniProt for this protein.

In Alzheimer's disease, CPLX2 is significantly downregulated in post-mortem brain tissue compared to age-matched controls, with a mean log2 fold-change of −1.035 across subcellular fractions in TMT-labeled proteomics analysis (Chaparral AD proteomics). This reduction may contribute to impaired synaptic transmission and vesicle dynamics that characterize AD pathology.