MECP2 gene mutations are the cause of most cases of Rett syndrome, a progressive neurologic developmental disorder and one of the most common causes of cognitive disability in females.

[9] MECP2 protein is found in all cells in the body, including the brain, acting as a transcriptional repressor and activator, depending on the context.

[10] In the brain, it is found in high concentrations in neurons and is associated with maturation of the central nervous system (CNS) and in forming synaptic contacts.

MeCP2 prefers to bind to sites on the genome with a chemical alteration made to a cytosine (C) when it occurs in a particular DNA sequence, "CpG".

[12] Once bound, MeCP2 will condense the chromatin structure, form a complex with histone deacetylases (HDAC), or block transcription factors directly.

[15] Reduced expression of MECP2 in Mecp2+/- neural stem cells causes an increase in senescence, impairment of proliferative capacity and accumulation of unrepaired DNA damage.

Rett syndrome is mainly found in girls with a prevalence of around 1 in every 10,000; male fetuses with normal karyotypes afflicted with this condition rarely survive to term and if so, usually die shortly after birth.

Patients are born with very hard to find signs of a disorder, but after about six months to a year and half, speech and motor function capabilities start to decrease.

Mutations in the gene have also been found in males with severe brain dysfunction (neonatal encephalopathy) who live only into early childhood.

Lastly, MECP2 mutations or changes in the gene's activity have been reported in some cases of autism (a developmental disorder that affects communication and social interaction).

The genetic loss of MECP2 has been identified as changing the properties of cells in the locus ceruleus, the exclusive source of noradrenergic innervation to the cerebral cortex and hippocampus.

[23] Researchers have concluded that "Because these neurons are a pivotal source of norepinephrine throughout the brainstem and forebrain and are involved in the regulation of diverse functions disrupted in Rett syndrome, such as respiration and cognition, we hypothesize that the locus ceruleus is a critical site at which loss of MECP2 results in CNS dysfunction.

Specifically, males express less MeCP2 than females,[26] and this aligns with the steroid-sensitive time period of the neonatal rat brain.

MeCP2 appears to regulate arginine vasopressin (AVP) and androgen receptor (AR) production in male rats but not in females.

Male rats with reduced MeCP2 levels also show a significant reduction of AR at two weeks following infusion, but this effect is gone by adulthood.

Vasopressin is a primary hormone involved in the Hypothalmic-Pituitary-Adrenal Axis, the connectivity in the brain that regulates processing of and reaction to stress.