FCN3 (Ficolin-3) is a calcium-dependent lectin that functions as a pattern recognition receptor in the innate immune system, specifically initiating the lectin pathway of complement activation 1. The protein recognizes and binds carbohydrates including N-acetylglucosamine, N-acetylgalactosamine, and D-fucose on pathogen surfaces, leading to complement activation and pathogen clearance 1. FCN3 has the highest complement-activating capacity among ficolins and is primarily synthesized in the liver and lung 2. Beyond its immune function, FCN3 demonstrates significant tumor suppressor activity in hepatocellular carcinoma (HCC). FCN3 expression is markedly downregulated in HCC tissues and associated with better patient survival 32. Mechanistically, FCN3 promotes ferroptosis by binding insulin receptor β and suppressing MUFA synthesis, while also inducing apoptosis through p53 pathway activation via SBDS-mediated ribosomal stress 45. The FCN3 gene exhibits polymorphisms affecting protein levels and function, including a frameshift mutation (1637delC) leading to complete ficolin-3 deficiency, which is associated with immunodeficiency 67. FCN3 deficiency represents a rare but clinically significant immune disorder, with only four cases of complete deficiency reported worldwide 7.