ADAM23 is a non-catalytic transmembrane metalloprotease-like protein predominantly expressed in the nervous system that functions as a synaptic adhesion molecule and trans-synaptic bridge 1. As a presynaptic protein, ADAM23 interacts with the secreted ligand LGI1 to modulate neuronal excitability and excitatory neurotransmission 2. Activity-driven translocation of LGI1 through its binding to ADAM23 facilitates trans-synaptic connections that adjust glutamatergic transmission proportionally to synaptic firing history 3. ADAM23 expression is developmentally regulated, with isoforms showing distinct temporal patterns during brain development, suggesting roles in neural development and synaptogenesis 4. The protein undergoes constitutive endocytosis and recycling with extended plasma membrane stability, supporting its receptor functions 5. Genetically, biallelic ADAM23 variants cause neonatal-onset epilepsy and myopathy, while genetic variants are associated with early neurological instability after ischemic stroke through excitotoxicity mechanisms 62. Beyond neurology, ADAM23 promoter hypermethylation occurs in colorectal and other cancers, suggesting tumor suppressor functions in cell adhesion and matrix interactions 7. These findings establish ADAM23 as a critical synaptic mediator of neuronal excitability with clinical relevance to epilepsy, stroke recovery, and cancer progression.