The Ca2+-calmodulin dependent protein kinase kinase-2 (CaMKK2) is a major transducer of Ca2+-signalling in cells, and a key regulator of brain function. CaMKK2 is activated by the Ca2+-Calmodulin complex in response to physiological stimuli that increase intracellular Ca2+, including membrane depolarization, glutamate (NMDA) receptor activation, and the appetite-regulating hormone ghrelin. We recently discovered that, in addition to Ca2+-calmodulin, CaMKK2 is also allosterically activated by long chain fatty acyl-coenzyme-A esters (LCFA-CoA) with a fatty acid chain length between 14 and 16 carbons (i.e. myristoyl-CoA and palmitoyl-CoA). Palmitoyl-CoA was the most effective activator among the LCFA-CoAs tested, and activated CaMKK2 with a half-maximal concentration of 470 nM, which is within the physiological range and below its critical micelle concentration. However, the structural basis of this newfound allosteric mechanism is poorly understood and there are no structures of CaMKK2 beyond the kinase domain, representing a significant gap in the field. CaMKK2 has been reported to associate with the scaffolding protein IQGAP1 in cells. We have confirmed this interaction and discovered that in addition to its scaffolding function, CaMKK2 is also allosterically activated by IQGAP1. Given the functional interaction between IQGAP1 and CaMKK2, we are actively working to solve the structure of this complex by cryo-EM. Our findings have uncovered novel allosteric mechanisms that regulates CaMKK2 activity and furthered our understanding of the interaction between IQGAP1 and CaMKK2.