CCDC34 (coiled-coil domain containing 34) has dual biological roles: a primary physiological function in spermatogenesis and an oncogenic function in multiple cancers. Physiologically, CCDC34 is essential for sperm flagella formation through regulation of anterograde intraflagellar transport; biallelic mutations cause multiple morphological abnormalities of sperm flagella (MMAF) with oligoasthenoteratozoospermia and male infertility 1. At the molecular level, CCDC34 deficiency disrupts axoneme organization and reduces intraflagellar transport-B complex proteins 1. Pathologically, CCDC34 functions as an oncogene across multiple cancer types. In lung adenocarcinoma, CCDC34 promotes stemness through β-catenin-mediated ATG5-induced autophagy, driving EGFR-TKI resistance 2. In lower-grade gliomas, elevated CCDC34 associates with advanced grade, recurrence, and poor survival through PI3K-Akt, HIF-1, and Notch pathways; DNA methylation (cg19157696) negatively regulates its expression 3. In bladder cancer, colorectal cancer, and esophageal squamous cell carcinoma, CCDC34 overexpression promotes proliferation, inhibits apoptosis, and enhances invasion via MAPK/ERK and PI3K/Akt signaling [PMID:26312564; 4; 56]. In hepatocellular carcinoma, the RABL2A-CCDC34 axis mediates sorafenib resistance through p38/JNK signaling 6. CCDC34 represents both a prognostic biomarker and potential therapeutic target for cancer treatment.