The CAMK protein family: Pivotal roles in calcium-dependent disease pathways and emerging therapeutic strategies.

Calmodulin (CAM) is a highly conserved calcium ion sensor in eukaryotic cells. Its molecule contains four EF-hand domains, which can respond to changes in intracellular calcium ion concentration and conduct signals. As the core mediator of calcium signals, CAM further activates the downstream Calcium/calmodulin-dependent protein kinases (CAMK) family. CAMK is a type of serine/threonine protein kinase with catalytic and regulatory domains. Its classical activation method is the formation of a complex between intracellular calcium ions and CAM and binding to the regulatory domain of CAMK, inducing conformational changes, thereby phosphorylating downstream effect proteins. Besides calcium ions, its activity can also be regulated by small molecules such as citric acid. In the field of oncology, CAMK2 is overexpressed in various malignant tumors such as non-small cell lung cancer and colorectal cancer, and is closely related to tumor proliferation, invasion, and poor prognosis. The mechanism involves regulating tumor stem cells and AMPK and other signaling pathways. In addition, the CAMK family also participates in inflammatory responses by regulating NF-κB and intervenes in metabolic processes such as glycolysis and fatty acid β-oxidation, thereby playing a role in immune diseases and metabolic disorders. In summary, the CAMK family serves as a key hub of calcium signals and is widely involved in the processes of cardiovascular diseases, tumors, immune abnormalities, and metabolic disorders. In-depth exploration of its structure and regulatory mechanisms will provide new targets and strategies for the treatment of related diseases.