Once bound to Ca2+, calmodulin acts as part of a calcium signal transduction pathway by modifying its interactions with various target proteins such as kinases or phosphatases.

[6] In the Ca2+-free state, the helices that form the four EF-hands are collapsed in a compact orientation, and the central linker is disordered;[5][6][7][8] in the Ca2+-saturated state, the EF-hand helices adopt an open orientation roughly perpendicular to one another, and the central linker forms an extended alpha-helix in the crystal structure,[5][6] but remains largely disordered in solution.

Calmodulin's ability to recognize a tremendous range of target proteins is due in large part to its structural flexibility.

[13] In addition to the flexibility of the central linker domain, the N- and C-domains undergo open-closed conformational cycling in the Ca2+-bound state.

[9] Calmodulin also exhibits great structural variability, and undergoes considerable conformational fluctuations, when bound to targets.

[23] This influence of target binding on Ca2+ affinity is believed to allow for Ca2+ activation of proteins that are constitutively bound to calmodulin, such as small-conductance Ca2+-activated potassium (SK) channels.

Similarly, Ca2+ may itself be displaced by other metal ions, such as the trivalent lanthanides, that associate with calmodulin's binding pockets even more strongly than Ca2+.

[30][31][26] Calmodulin mediates many crucial processes such as inflammation, metabolism, apoptosis, smooth muscle contraction, intracellular movement, short-term and long-term memory, and the immune response.

It does this by binding various targets in the cell including a large number of enzymes, ion channels, aquaporins and other proteins.

Calmodulin can undergo post-translational modifications, such as phosphorylation, acetylation, methylation and proteolytic cleavage, each of which has potential to modulate its actions.

Calcitonin is a polypeptide hormone that lowers blood Ca2+ levels and activates Gs protein cascades that leads to the generation of cAMP.

[37] Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a crucial role in a type of synaptic plasticity known as long-term potentiation (LTP) which requires the presence of calcium/calmodulin.

Ca2+ pulses created due to increased influx and efflux act as cellular signals in response to external stimuli such as hormones, light, gravity, abiotic stress factors and also interactions with pathogens.

Arabidopsis thaliana contains about 50 different CML genes,[41] which leads to the question of what purpose these diverse ranges of proteins serve in the cellular function.

In Arabidopsis, the protein DWF1 plays an enzymatic role in the biosynthesis of brassinosteroids, steroid hormones in plants that are required for growth.

There is a Ca2+ flux at the tip of the root hair initially followed by repetitive oscillation of Ca2+ in the cytosol and also Ca2+ spike occurs around the nucleus.

Ca2+ signatures of this nature usually activate the plant defense system by inducing defense-related genes and the hypersensitive cell death.

CaMs, CMLs and CaM-binding proteins are some of the recently identified elements of the plant defense signaling pathways.

Mutations in the CaM binding proteins can lead to severe effects on the defense response of the plants towards pathogen infections.

Change in intracellular Ca2+ levels is used as a signature for diverse responses towards mechanical stimuli, osmotic and salt treatments, and cold and heat shocks.

In response to external stress CaM activates glutamate decarboxylase (GAD) that catalyzes the conversion of L-glutamate to GABA.

The CaMBP genes expressed in the sorghum are depicted as a “model crop” for researching the tolerance to heat and drought stress.

In an Arabidopsis thaliana study, hundreds of different proteins demonstrated the possibility to bind to CaM in plants.