Thus, the “genie” that sparks our remarkable cognitive abilities also renders us vulnerable to cognitive disorders when regulatory proteins are unanchored or lost, and the “genie” can no longer be put back in the “bottle.” Dysregulated calcium–cAMP signaling can lead to a number of detrimental actions, including excessive opening of K+ channels that reduce neuronal firing, mitochondrial changes that drive inflammation and loss of synapses, and activation of kinases that induce tau pathology and degeneration. Here, MAPT is linked to cognitive disorder.