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).

[9] 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.

The human protein is very similar to the one that is found in mice (they are 92% identical at amino acid level, this enabling the scientists to study its structure.

There are other CAM proteins like Ng-CAM (found in chicken) which has lower similarities to the human one (they are 40% identical at the amino acid level).

L1 is also involved in synaptic plasticity, which is the ability of synapses to strengthen or weaken, and it also plays a role in regeneration after trauma.

Lower limb spasticity, mental retardation, hydrocephalus and flexion deformity of the thumbs are some of the symptoms expressed mostly in male individuals who suffer from this condition.

These mutations mostly affect structurally important key residues in the extracellular region of L1 causing alterations in the protein binding properties, which correlate to the impairment of neuronal physiological mechanisms such as cell adhesion or specific interacting with other molecules.

Furthermore, evidence shows there is a correlation between fetal alcohol spectrum disorder and L1 protein since ethanol inhibits L1-mediated adhesion and neurite outgrowth.

They are also important in the formation of heterophilic interactions with NCAM, TAG-1, F11 and receptor tyrosine kinases (specially during the development of the nervous system).

The six Ig motif of the L1 protein contains an Arg-Gly-Asp sequence which allows binding with diverse surface cell integrins.

The interaction is held in high-affinity binding sites located within the so-called “ank repeats” also known as membrane-binding domains.

Also, L1 protein cytoplasmic tail can bind adaptor 2 (ADP), a key component of clathrin mediated endocytosis.

It has been seen this protein plays a key role in inflammatory reactions as the ones taking place in the tissue surrounding a tumor.

Once tumor cells become anchorage-independent and migratory, due to L1 up-regulation, they leave the tissue where they belong and migrate through the capillaries to other organs.

However, recent studies have noted these cancer cells overproduce anti-PA serpins, which are the usual inhibitors of plasmin, allowing them to cross the BBB and succeed in metastasis.

[37] Because L1CAM is considered to be a key factor in metastasis, it has been suggested that blocking this protein may inhibit cancer cells migration and tumor progression.

Antibody therapy directed against L1CAM in mice models of cancer block tumor growth but enhance EMT.

[38] Liposome-encapsulated small interfering RNA has also proved to be an effective inhibitor for L1CAM expression as its function is to degrade a specific range of mRNA base pairs (in this case, the ones encoding for L1CAM sequence of amino acids) after transcription, so that the protein cannot be synthetised.