CYLC1 encodes cylicin 1, a testis-specific, lysine-rich cytoskeletal protein that plays a critical role in male fertility by establishing normal sperm morphology during spermiogenesis 1. The primary function of CYLC1 is to anchor the acrosome to the nuclear envelope through formation of an 'inner acrosomal membrane-cylicins-nuclear envelope' sandwich structure, which requires interaction with other perinuclear theca proteins, the inner acrosomal membrane protein SPACA1, and the nuclear envelope protein FAM209 2. Loss of cylicin-1 in mice causes high incidence of malformed sperm heads with acrosome detachment from the nucleus, decreased epididymal sperm counts, impaired cytoplasm shedding, and reduced sperm motility 1. CYLC1 variants are significantly associated with male infertility due to sperm head deformity in humans. Whole exome sequencing identified multiple CYLC1 pathogenic variants in infertile men with sperm morphological abnormalities, including altered CYLC1 localization and acrosomal defects 32. Notably, patients carrying CYLC1 variants achieved successful pregnancies through intracytoplasmic sperm injection (ICSI), suggesting therapeutic options for affected individuals 3. CYLC1 is positioned as an important diagnostic marker in the male infertility proteome 4.