Ca²⁺/calmodulin-dependent protein kinase kinases (CaMKKs) were originally identified as a member of the calmodulin (CaM) kinase (CaMK) family, which phosphorylate and activate AMPK and two multifunctional CaMKs including CaMKI and CaMKIV, constituting Ca²⁺-dependent kinase cascades named CaMK cascades. We have developed a CaMKK inhibitor, STO-609 and TIM-063 to evaluate physiological and pathophysiological function(s) of CaMKK-mediated Ca²⁺-signal transduction. Now, we knew CaMK cascades are involved in various cellular responses including neuronal activity, metabolic regulation and cancer cell growth.