ADAM22 is a non-catalytic metalloprotease-like protein 1 that functions as a neuronal receptor for the secreted ligand LGI1 2. In the brain, ADAM22 is highly expressed 3 and serves as a probable integrin ligand involved in cell adhesion regulation 3. The LGI1-ADAM22 complex forms a trans-synaptic hub within PSD-95-containing postsynaptic protein complexes, where it is essential for AMPA and NMDA receptor-mediated synaptic transmission and synaptic plasticity 2. ADAM22 activates integrin β1 through its disintegrin domain to promote cellular proliferation and migration 4. Biallelic ADAM22 variants cause developmental and epileptic encephalopathy (DEE) characterized by neonatal/infantile-onset seizures and global developmental delay 5. The LGI1-ADAM22 pathway dysregulation underlies multiple synaptic disorders; monoallelic LGI1 mutations cause autosomal dominant lateral temporal lobe epilepsy, while autoantibodies against LGI1 cause limbic encephalitis with memory loss and seizures 6. Beyond neurology, ADAM22 expression is elevated in endocrine-resistant breast cancer and pituitary adenoma, where LGI1-based therapies may provide therapeutic benefit 7. ADAM22 represents a critical regulator of synaptic function and a potential drug target for neurological and oncological diseases.