CLTA (clathrin light chain A) is a critical component of clathrin-coated vesicles that functions primarily in endocytosis and cellular transport. CLTA facilitates the uptake of small extracellular vesicles (sEVs) through clathrin-mediated endocytosis, playing a crucial role in intercellular communication 1. The gene is located on chromosome 9-q24 and undergoes alternative mRNA splicing to generate tissue-specific protein isoforms, with neuron-specific insertions encoded by discrete exons 2. In hepatocellular carcinoma (HCC), CLTA is significantly overexpressed in tumor tissues and its expression progressively increases with tumor stage 1. CLTA enhances cancer cell proliferation, motility, and invasiveness by increasing CAPG expression to facilitate sEV uptake 1. Additionally, HCC-derived sEV-CLTA remodels the microvascular niche by stabilizing basigin (BSG), promoting angiogenesis and endothelial dysfunction 3. CLTA has emerged as a potential diagnostic biomarker and therapeutic target, with CLTA inhibitor Pitstop 2 showing efficacy in patient-derived xenograft models 13. The protein has also been identified as a diagnostic marker for postmenopausal osteoporosis and thyroid cancer, indicating its broader clinical significance across multiple diseases 45.