FOXP2 is a member of the forkhead box family of transcription factors, proteins that regulate gene expression by binding to DNA.

The forkhead box P2 protein is active in the brain and other tissues before and after birth, and many studies show that it is paramount for the growth of nerve cells and transmission between them.

[18] Knockout mice with no functional copies of FOXP2 are runted, display abnormalities in brain regions such as the Purkinje layer, and die an average of 21 days after birth from inadequate lung development.

[12] Evidence from genetically manipulated mice[24] and human neuronal cell models[25] suggests that these changes affect the neural functions of FOXP2.

The FOXP2 gene has been implicated in several cognitive functions including; general brain development, language, and synaptic plasticity.

[17][27][29][26][30][31] There is some evidence that the linguistic impairments associated with a mutation of the FOXP2 gene are not simply the result of a fundamental deficit in motor control.

Brain imaging of affected individuals indicates functional abnormalities in language-related cortical and basal ganglia regions, demonstrating that the problems extend beyond the motor system.

[33] A 2020 genome-wide association study (GWAS) implicates single-nucleotide polymorphisms (SNPs) of FOXP2 in susceptibility to cannabis use disorder.

A heterozygous nonsense mutation, R328X variant, produces a truncated protein involved in speech and language difficulties in one KE individual and two of their close family members.

When tasked with repetition and verb generation, these individuals with DVD/CAS had decreased activation in the putamen and Broca's area in fMRI studies.

[8] These findings suggest that the effects of FOXP2 are not limited to motor control, as they include comprehension among other cognitive language functions.

[27] While FOXP2 has been proposed to play a critical role in the development of speech and language, this view has been challenged by the fact that the gene is also expressed in other mammals as well as birds and fish that do not speak.

[47] Other researchers offer alternative explanations for how the H. sapiens version would have appeared in Neanderthals living 43,000 years ago.

[56] Researchers deduced that there could also be further clinical applications in the direction of these studies in regards to illnesses that show effects on human language ability.

[24] When FOXP2 expression was altered in mice, it affected many different processes including the learning motor skills and the plasticity of synapses.

FOXP2 was also found in the medial geniculate nucleus of the mouse brain, which is the processing area that auditory inputs must go through in the thalamus.

The negative effects of the mutations of FOXP2 in these brain regions on motor abilities were shown in mice through tasks in lab studies.

When analyzing the brain circuitry in these cases, scientists found greater levels of dopamine and decreased lengths of dendrites, which caused defects in long-term depression, which is implicated in motor function learning and maintenance.

There is further evidence for mutations of targets of the FOXP2 gene shown to have roles in schizophrenia, epilepsy, autism, bipolar disorder and intellectual disabilities.

[10][60] Gene knockdown of FOXP2 in area X of the basal ganglia in songbirds results in incomplete and inaccurate song imitation.

This overexpression produced similar effects to that of knockdown; juvenile zebra finch birds were unable to accurately imitate their tutors.

In zebrafish, FOXP2 is expressed in the ventral and dorsal thalamus, telencephalon, diencephalon where it likely plays a role in nervous system development.

[64] In 1990, Myrna Gopnik, Professor of Linguistics at McGill University, reported that the disorder-affected KE family had severe speech impediment with incomprehensible talk, largely characterized by grammatical deficits.

[65] She hypothesized that the basis was not of learning or cognitive disability, but due to genetic factors affecting mainly grammatical ability.

This is one of the few known examples of Mendelian (monogenic) inheritance for a disorder affecting speech and language skills, which typically have a complex basis involving multiple genetic risk factors.

[70] In 1998, Oxford University geneticists Simon Fisher, Anthony Monaco, Cecilia S. L. Lai, Jane A. Hurst, and Faraneh Vargha-Khadem identified an autosomal dominant monogenic inheritance that is localized on a small region of chromosome 7 from DNA samples taken from the affected and unaffected members.

[6] Around this time, the researchers identified an individual who was unrelated to the KE family but had a similar type of speech and language disorder.

[7] Using a combination of bioinformatics and RNA analyses, they discovered that the gene codes for a novel protein belonging to the forkhead-box (FOX) group of transcription factors.