CIB4 (calcium and integrin binding family member 4) is a calcium- and magnesium-binding protein characterized by canonical EF-hand motifs 1. The protein binds divalent cations (Ca2+ and Mg2+), which induce conformational changes in secondary and tertiary structures, and interacts with integrin αIIb subunits, suggesting involvement in integrin signaling regulation 2. CIB4 exhibits testis-specific expression 3, with two alternatively spliced variants (L-CIB4 and S-CIB4) identified in sheep, with S-CIB4 potentially linked to breed fecundity 4. The gene is highly conserved across mammals, showing 96-100% nucleotide identity with other species 3. Clinically, CIB4 is implicated in male fertility and infertility. Decreased CIB4 expression in testicular tissue of nonobstructive azoospermia patients and in sperm of oligoasthenozoospermic patients correlates positively with sperm progressive motility and viability 5. CIB4 variants are also associated with visceral leishmaniasis susceptibility 6. These findings suggest CIB4 plays essential roles in spermatogenesis and sperm function, making it a potential biomarker and therapeutic target for male infertility treatment.