Structure-Function Diversity of Calcium-Binding Proteins (CaBPs): Key Roles in Cell Signalling and Disease

Calcium (Ca²⁺) signalling is a fundamental cellular process, essential for a wide range of physiological functions. It is regulated by various mechanisms, including a diverse family of Ca²⁺-binding proteins (CaBPs), which are structurally and functionally similar to calmodulin (CaM). The CaBP family consists of six members (CaBP1, CaBP2, CaBP4, CaBP5, CaBP7, and CaBP8), each exhibiting unique localisation, structural features, and functional roles. In this review, we provide a structure-function analysis of the CaBP family, highlighting the key similarities and differences both within the family and in comparison to CaM. It has been shown that CaBP1-5 share similar structural and interaction characteristics, while CaBP7 and CaBP8 form a distinct subfamily with unique properties. This review of current CaBP knowledge highlights the critical gaps in our understanding, as some CaBP members are less well characterised than others. We also examine pathogenic mutations within CaBPs and their functional impact, showing the need for further research to improve treatment options for associated disorders.