Reelin, encoded by the RELN gene, is a large secreted extracellular matrix glycoprotein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates synaptic plasticity by enhancing the induction and maintenance of long-term potentiation.

Reelin has been suggested to be implicated in pathogenesis of several brain diseases. The expression of the protein has been found to be significantly lower in schizophrenia and psychotic bipolar disorder, temporal lobe epilepsy and autism.

Reelin's name comes from the abnormal reeling gait of reeler mice, and by the few extant Cajal-Retzius cells. Among GABAergic interneurons, reelin seems to be detected predominantly in those expressing calretinin and calbindin, like bitufted, horizontal, and Martinotti cells, but not parvalbumin-expressing cells, like chandelier or basket neurons. and changes to gene regulatory networks that control cell migration suggests a potential link between altered reelin expression in patient brain tissue to disrupted cell migration during brain development. To model the role of reelin in the context of schizophrenia at a cellular level, olfactory neurosphere-derived cells were generated from the nasal biopsies of schizophrenia patients, and compared to cells from healthy controls. when compared to healthy control cells, but expresses the key reelin receptors and DAB1 accessory protein.

Reelin was originally in 2001 implicated in a study finding associations between autism and a polymorphic GGC/CGG repeat preceding the 5' ATG initiator codon of the RELN gene in an Italian population. Longer triplet repeats in the 5' region were associated with an increase in autism susceptibility.

Other conditions

One genome-wide association study indicates a possible role for RELN gene variation in otosclerosis, an abnormal growth of bone of the middle ear. A 2020 study from UT Southwestern Medical Center suggests circulating Reelin levels might correlate with MS severity and stages, and that lowering Reelin levels might be a novel way to treat MS.

Factors affecting reelin expression

[[File:Differential reelin levels in the cortex of adult high and low LG rats.gif|thumb|330px|Increased cortical reelin expression in the pups of "High LG" (licking and grooming) rats. A figure from Smit-Righter et al., 2009

According to the epigenetic hypothesis, drugs that shift the balance in favour of demethylation have a potential to alleviate the proposed methylation-caused downregulation of RELN and GAD67. In one study, clozapine and sulpiride but not haloperidol and olanzapine were shown to increase the demethylation of both genes in mice pretreated with l-methionine.

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Further reading

  • Human RELN at WikiGenes