The AMP-activated protein kinase (AMPK) is an αβγ heterotrimer that is activated by low cellular energy status and affects a switch away from energy-requiring processes and toward catabolism [1]. While it is primarily regulated by AMP and ATP, high muscle glycogen has also been shown to repress its activation [2, 3]. Mutations in the γ2 and γ3 subunit isoforms lead to arrhythmias associated with abnormal glycogen storage in human heart [4–7] and elevated glycogen in pig muscle [8], respectively. A putative glycogen binding domain (GBD) has now been identified in the β subunits. Coexpression of truncated β subunits lacking the GBD with α and γ subunits yielded complexes that were active and normally regulated. However, coexpression of α and γ with full-length β caused accumulation of AMPK in large cytoplasmic inclusions that could be counterstained with anti-glycogen or anti-glycogen synthase antibodies. These inclusions were not affected by mutations that increased or abolished the kinase activity and were not observed by using truncated β subunits lacking the GBD. Our results suggest that the GBD binds glycogen and can lead to abnormal glycogen-containing inclusions when the kinase is overexpressed. These may be related to the abnormal glycogen storage bodies seen in heart disease patients with γ2 mutations.