Calmodulin and Calmodulinopathies.

The universal calcium sensor calmodulin decodes calcium signals by translating calcium ion fluctuations to protein-level responses. Consequently, calmodulin couples calcium signals to a multitude of physiological functions. Calmodulin interacts with an extensive network of proteins, some of which harbor calmodulin as a constitutively bound subunit, whereas others recruit calmodulin in response to a calcium signal. Depending on cellular context, calmodulin can either amplify or dampen calcium signals through positive and negative regulatory mechanisms. This multifaceted nature of calmodulin signaling requires meticulous control, which is conferred by sophisticated genetic and protein-level architecture. The physiological importance of calmodulin is underscored by the discovery of rare and life-threatening pathogenic mutations with a complex phenotypic spectrum.