The AMP-activated protein kinase is an evolutionarily conserved hetero-trimer that is important for metabolic sensing in all eukaryotes. The muscle-specific isoform of the regulatory c-subunit of the kinase, AMP-activated protein kinasec3, has a key role in glucose and fat metabolism in skeletal muscle, as suggested by metabolic characterization of humans, pigs and mice harboring substitutions in the AMP-binding Bateman domains ofc3.