CCDC181 is a microtubule-binding protein essential for male germ cell development and ciliary function. During spermatogenesis, CCDC181 localizes to the microtubular manchette of elongating spermatids, where it interacts with Hook1 to facilitate proper sperm head shaping and flagellum formation 1. The protein also localizes to sperm flagella and the basal half of motile cilia, with RNA expression restricted primarily to haploid germ cells but also present in ciliated somatic tissues 1. CCDC181 functions as a high-abundance axonemal component in human airway cilia 2 and may mediate ciliary motility through interactions with protein phosphatase 1 catalytic subunits 1. Clinically, CCDC181 has emerged as a promising DNA methylation biomarker for cancer prognosis. Aberrant CCDC181 promoter hypermethylation and downregulation are associated with aggressive prostate cancer 34, lung adenocarcinoma 567, and HPV-related oropharyngeal squamous cell carcinoma 8. Integration of CCDC181 methylation status with clinical variables significantly improves prognostic prediction in lung adenocarcinoma, with potential applications for early diagnosis and personalized targeted therapy.