Gilles de la Tourette syndrome (TS) is a complex neuropsychiatric disorder characterized by the presence of multiple, involuntary motor and vocal tics that fluctuate in severity. The disorder is associated with a high prevalence of comorbid disorders including Autism Spectrum Disorder (ASD). Its high heritability and largely unknown genetic etiology has motivated intense research towards identifying the genetic basis of the disorder. Documentation of chromosomal abnormalities, linkage studies and candidate gene association studies have so far been able to implicate several disorder-associated genes with most evidence supporting SLITRK1, IMMP2L, CNTNAP2, NLGN4X and HDC. CNTNAP2, NLGN4X and SLITRK1 have been implicated in synaptic dysfunction due to the location of the proteins, which function at the neuronal synapse. IMMP2L is located on the mitochondrial inner membrane and has an incompletely characterized function. To date, little evidence has been found associating IMMP2L with a principal functional role in astrocytes.

The LRRN3 gene, which encodes a leucine-rich repeat protein is transcribed anti-sense to the third intron of IMMP2L. Expression of LRRN3 is enriched within the brain and there is evidence for the association of LRRN3 with ASD. Consequently the functional relationship between the nested genes may have a significant implication on the understanding of TS and ASD.

Here we investigated the role of IMMP2L in mitochondrial function in human primary astrocytes and whether transcription through IMMP2L regulates LRRN3 expression.