C4BPA encodes the alpha chain of complement component 4 binding protein (C4BP), a hepatic-derived plasma glycoprotein that negatively regulates the classical complement pathway 1. The protein functions as a cofactor for C3b/C4b inactivator, facilitating hydrolysis of complement fragment C4b and accelerating degradation of the C3 convertase complex C4bC2a 1. C4BPA expression is controlled by the hepatic transcription factor HNF1 through a TATA-less promoter mechanism 1. During acute phase responses, C4BPA expression is differentially modulated by cytokines (IL-6, IL-1β, IFN-γ upregulate; TNF-α downregulates), enabling dynamic adjustment of complement regulation 2. Beyond complement control, emerging evidence implicates C4BPA in pathological inflammation and malignancy. C4BPA is upregulated in spinal dural arteriovenous fistula cerebrospinal fluid (area under ROC curve 0.86) and correlates with acute inflammatory response activation 3. Genetically validated studies identify C4BPA as a druggable target in non-small cell lung cancer, promoting progression via the CCL8 inflammatory chemokine axis 4, and in delirium, where C4BPA explains 16.7% of aging-related risk 5. In gastric cancer, tumor-derived C4BPA drives disease progression by promoting M2-like macrophage polarization through the C5a-C5aR1-STAT3 immunomodulatory pathway 6. These findings position C4BPA as both a complement regulator and inflammatory oncology target.