Methyl-CpG-binding protein 2 (MeCP2) is a chromosomal protein that binds to methylated DNA. MeCP2 can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. MeCP2 mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A. Defects in MeCP2 are linked to Angelman syndrome (AS), also known as happy puppet syndrome. AS is a neurodevelopmental disorder characterized by severe mental retardation, absent speech, ataxia, sociable affect and dysmorphic facial features. AS and Rett syndrome have overlapping clinical features. Phosphorylation and dephosphorylation of Ser80 is involved in modulating the dynamic function of MECP2 in neurons transiting between resting and active states within neural circuits that underlie behaviors.