AMP activated protein kinase (AMPK) was identified as a result of its phosphorylation and inactivation of lipid metabolism enzymes. However, AMPK also phosphorylates enzymes involved in other metabolic pathways. AMPK is activated by AMPKK (AMPK Kinase)-mediated phosphorylation in response to intracellular changes in AMP levels. Although rat skeletal muscle AMPK exists as a monomer, active rat liver AMPK is a heterotrimer of α (catalytic subunit), β, and γ subunits. The catalytic subunit (63 kDa) is structurally and functionally related to the S. cerevisiae SNF1 protein kinase, an enzyme that is required for expression of glucose repressed genes during glucose starvation. AMPK β (38 kDa) is strongly related to SIP2 (35% identity) and contains a C-terminal region that is very homologous to the SIP1/SIP2/GAL83 ASC domain. AMPK β has some identity (35%) with SNF4, which is necessary for SNF1 activation. Both AMPK β and γ are widely expressed in rat tissues. AMPK β facilitates the interactions of the α and γ subunits in vitro. Although AMPK β is clearly necessary for formation of the heterotrimeric complex, there are other probably, yet unknown, roles for this protein.