The p90 ribosomal S6 kinases (RSKs) comprise a family of serine/threonine kinases that lie at the terminus of the ERK pathway. In humans, the RSK family consists of four isoforms (RSK1 to –4). RSK family members are unusual among serine/threonine kinases in that they contain two distinct kinase domains, both of which are catalytically functional. Theses kinase dimains are activated in a sequential manner by a series of phosphorylations. RSK regulates gene expression via association and phosphorylation of transcriptional regulators including c-Fos, estrogen receptor, NFkappaB/IkappaB alpha, cAMP-response elementbinding protein (CREB).