C8G (complement C8 gamma chain) is a component of the membrane attack complex (MAC), a multiprotein assembly that executes complement-mediated cell lysis 1. Located on chromosome 9.3 2, C8G belongs to the lipocalin protein family 2 and functions as part of the C5b8 intermediate complex alongside C8A, C8B, C5b, C6, and C7 3. During MAC assembly, C8G inserts into target cell membranes and increases membrane rigidity, though it does not form pores independently 3. The MAC is activated through multiple complement pathways (classical, alternative, lectin, and GZMK) following C5 proteolytic cleavage, ultimately leading to target cell membrane rupture and lysis 3. Clinically, C8G dysregulation associates with multiple diseases. Elevated urinary C8G levels correlate with systemic lupus erythematosus activity and serve as a non-invasive biomarker (AUC 0.736) 4. C8G expression increases in tubular tissues of autoimmune-related kidney diseases, suggesting involvement in the complement-mitochondrial-EMT pathway contributing to renal damage 5. Inverse associations exist between C8G levels and primary sclerosing cholangitis risk 6, and elevated C8G in astrocyte-derived exosomes associates with cognitive impairment in obstructive sleep apnea patients 7. Hepatic HNF4α regulates C8G transcription, indicating its importance for MAC formation 8.