The calcium- and integrin-binding protein (CIB) family, comprising four evolutionarily conserved members (CIB1, CIB2, CIB3, and CIB4), is characterized by canonical EF-hand motifs. The functions of CIBs in the inner ear have been investigated, although further research is still necessary to gain a comprehensive understanding of them. Among the CIB family members, CIB2 is essential for auditory function. CIB3 and CIB2 jointly participate in the regulation of balance. Beyond their sensory roles, CIBs exhibit multifunctionality through calcium-dependent interactions with diverse molecular partners, contributing to the pathogenesis of various conditions, including neurological disorders, cardiovascular diseases, cancer, and male infertility. In this review, we discuss the conserved structure of the CIB family, highlighting its contributions to various biological functions. We also summarize the distribution and function of the CIB family, emphasizing the pivotal roles of CIB2 and CIB3 in hearing and balance.
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