CCDC42 (coiled-coil domain containing 42) is essential for male fertility through its critical role in sperm development and flagellum biogenesis. During spermiogenesis, CCDC42 localizes to the manchette and sperm tail, where it functions in the head-tail coupling apparatus (HTCA) development 1. The protein interacts with multiple partners including CFAP58, IFT88, and ODF2 to facilitate intraflagellar transport and proper cargo delivery during flagellar assembly 2. Loss-of-function mutations in Ccdc42 result in profound male infertility characterized by abnormal HTCA formation, lack of flagellated sperm, malformed flagella, and azoospermia in mice 1. CCDC42's testis-enriched expression pattern, with minimal expression outside the brain and developing sperm, makes it an ideal candidate for screening human male infertility cases caused by azoospermia 1. Beyond reproductive biology, CCDC42 variants have been associated with heroin addiction susceptibility in Han Chinese populations 3 and identified as genetic risk factors in triple-negative breast cancer in Indian populations 4, suggesting broader biological roles. Population-specific DNA methylation patterns at CCDC42 loci have been identified between African and European ancestry populations with potential disease relevance 5.