Members of the Jumonji domain 2 (JMJD2) family contain a JmjN domain, a JmjC domain, a JD2H domain, two TUDOR domains, and two PHD-type zinc fingers. The first member of this group, JMJD2A, is widely expressed in human tissues and cell lines and functions as a trimethylation-specific demethylase, converting specific trimethylated histone residues to the dimethylated form, and as a transcriptional repressor. JMJD2A can also form a complex with the androgen receptor (AR), a transcription factor that is pivotal for the development of prostate cancer. Overexpression of JMJD2A stimulates AR function and this stimulation is dependent on JMJD2A catalytic activity, suggesting that JMJD2A might be a critical protein with roles in cell proliferation and oncogenesis.