Neural cell adhesion molecule L1

L1CAM (neural cell adhesion molecule L1) is a transmembrane glycoprotein of 1257 amino acids that mediates cell–cell interactions critical to nervous system development and function (UniProt: P32004). It regulates neuronal migration, axonal growth, fasciculation, and synaptogenesis during development, and contributes to synaptic plasticity and neuronal structure dynamics in the mature brain. The protein interacts with tyrosine kinase receptors to generate intracellular signals governing these processes.

L1CAM dysfunction is associated with severe X-linked neurodevelopmental disorders, including congenital hydrocephalus, MASA syndrome, and partial agenesis of the corpus callosum (UniProt: P32004). These conditions feature intellectual disability, spasticity, and structural brain abnormalities resulting from impaired neuronal migration and axonal guidance during development.

In Alzheimer's disease, L1CAM is downregulated in post-mortem brain tissue relative to age-matched controls, with a mean log2 fold-change of −0.48 (Chaparral AD proteomics). This reduction was detected across subcellular fractions in a TMT-labeled proteomics study, suggesting altered cell adhesion dynamics may contribute to synaptic and neuronal degeneration in AD pathology.