KHDC1 (KH domain containing 1) is an RNA-binding protein localized to the cytoplasm that plays complex roles in cell proliferation and apoptosis regulation. As a member of the KHDC family, KHDC1A functions as a translational repressor through its KH domain, with N-terminal and C-terminal regions required for activity 1. The protein localizes to the endoplasmic reticulum and induces caspase-3-dependent apoptosis via ER-specific signaling pathways 1. In contrast, KHDC1L, another family member, promotes cell proliferation and inhibits apoptosis in head and neck squamous cell carcinoma (HNSCC) through PI3K-AKT and Bcl-2 pathways, elevating pAKT/AKT and Bcl-2 levels while decreasing Caspase-3 activity 2. KHDC1 represents a unique eutherian mammalian gene family with high expression in oocytes and reproductive tissues 1. Clinically, KHDC1 dysregulation is associated with multiple cancer types: KHDC1L overexpression in HNSCC suggests potential as a diagnostic and therapeutic target 2, while KHDC1 variants on chromosome 6 show genetic association with actinic keratosis risk 3. Additionally, eccDNA-derived KHDC1 sequences are aberrantly expressed in lung adenocarcinoma tissues 4, though their specific biomarker utility remains unclear.