CCIN encodes Calicin, a cytoskeletal protein essential for male fertility that functions primarily in sperm head morphogenesis during spermiogenesis. Calicin is required for formation and maintenance of the cytoskeletal calyx, a highly organized structure surrounding the sperm nucleus 1. The protein plays a critical role in nuclear and acrosomal shaping, with mutations in CCIN causing amorphous sperm head malformation 2. Mechanistically, CCIN-associated mutations result in markedly reduced Calicin levels and severe sperm head malformation, which prevents zona pellucida adherence—the likely primary mechanism of infertility 1. CCIN mutations cause teratozoospermia, a major category of male infertility characterized by structurally abnormal spermatozoa 1. Clinically, mutations in CCIN are associated with Spermatogenic Failure 91, and affected men exhibit severely compromised natural fertility. However, intracytoplasmic sperm injection (ICSI) successfully bypasses the zona adherence defect, enabling successful reproduction in affected couples 1. CCIN has also been identified as part of a male infertility gene network through transcriptomic and proteomic analyses 34, suggesting its importance in the broader molecular pathology of male factor infertility and highlighting its diagnostic value for genetic counseling.