L1, also known as L1CAM, is a transmembrane protein member of the L1 protein family, encoded by the L1CAM gene. This protein, of 200-220 kDa, is a neuronal cell adhesion molecule with a strong implication in cell migration, adhesion, neurite outgrowth, myelination and neuronal differentiation. It also plays a key role in treatment-resistant cancers due to its function. It was first identified in 1984 by M. Schachner who found the protein in post-mitotic mice neurons. Mutations in the L1 protein are the cause of L1 syndrome, sometimes known by the acronym CRASH (corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia and hydrocephalus). Tissue and cellular distribution L1 protein is located all over the nervous system on the surface of neurons. It is placed along the cellular membrane so that one end of the protein remains inside the nerve cell while the other end stays on the outer surface of the neurone. This position allows the protein to activate chemical signals which spread through the neurone. There are a wide variety of cells which express the protein L1, not only neuronal cells but also some non-neuronal ones. Cells which are known nowadays to express the protein L1 are: immature oligodendrocytes and Schwann cells, which are non-neuronal cells that provide support and protection for neurons and form myelin; T cells which are lymphocytes involved in cell-mediated immunity; other types of lymphocytes such as B cells and Monocytes. It is also expressed in intestinal epithelial progenitor cells, cerebellum neurons such as Cerebellum granule cell and Purkinje cells. Finally, it is expressed in multiple tumor cells for example Melanoma and lung carcinoma cells. L1CAM is also frequently used as a marker of Extracellular Vesicles (EVs) originating from neuronal cells, although its presence specifically on neuron-derived EVs is debatable. Gene The human L1CAM gene is found in X chromosome regions that are implicated in different neuromuscular diseases, and near the one associated with mental retardation. L1CAM gene is located in the long arm of X chromosome in Xq28 position. Structure The L1 cell adhesion molecule (L1CAM) is a cell surface glycoprotein found in humans (and other forms of life as mice, for example) which has a 1253 amino acid protein sequence. The extracellular portion is formed of six immunoglobulin domains followed by five fibronectin type III domains which are connected to a small intracellular domain by a transmembrane helix. The human protein is very similar to