Changes in intracellular free Ca(2+) concentration ([Ca(2+)](i)) affect many different aspects of neuronal function ranging from millisecond regulation of ion channels to long term changes in gene expression. These effects of Ca(2+) are transduced by Ca(2+)-binding proteins that act as Ca(2+) sensors by binding Ca(2+), undergoing a conformational change and then modifying the function of additional target proteins. Mammalian species express 14 members of the neuronal calcium sensor (NCS) family of EF hand-containing Ca(2+)-binding proteins which are expressed mainly in photoreceptor cells or neurons. Many of the NCS proteins are membrane targeted through their N-terminal myristoylation either constitutively or following exposure of the myristoyl group after Ca(2+) binding (the Ca(2+)/myristoyl switch). The NCS proteins have been implicated in a wide range of functional roles in neuronal regulation, several of which have been confirmed though molecular genetic analyses.