JMJD3 is a 1,679 amino acid nuclear protein that contains one JmjC domain and belongs to the highly conserved JmjC domain-containing protein family. Functioning as a histone demethylase, JMJD3 uses iron and ascorbate as cofactors to demethylate dimethylated and trimethylated Lys-27 residues of Histone H3, thereby playing an important role in the modification of the histone code. Additionally, JMJD3 regulates posterior development and is involved in the inflammatory response, specifically by mediating macrophage differentiation. JMJD3 is also thought to control the expression of neurogenesis-related proteins and, via this regulatory mechanism, may be necessary for neural commitment during early development. Two isoforms of JMJD3 exist due to alternative splicing events.