C1S encodes a serine protease component of the complement C1 complex that initiates the classical complement pathway 1. C1s functions as the catalytic enzyme within a calcium-dependent C1s-C1r-C1r-C1s tetramer that associates with the recognition protein C1q 1. Upon pathway activation, C1s catalyzes the specific cleavage of complement components C4 and C2, generating the C3 convertase critical for downstream complement cascade amplification 2. Beyond canonical complement activation, C1s cleaves insulin-like growth factor binding protein 5 (IGFBP5), thereby modulating IGF1 signaling. C1s deficiency represents a recognized disease state, and dysregulation of C1s has been implicated in epilepsy pathogenesis through altered immune response 3. The clinical significance of C1s inhibition is exemplified by sutimlimab, a monoclonal antibody that blocks C1s protease activity to prevent complement-mediated hemolysis in cold agglutinin disease patients 2. Additionally, elevated C1S expression correlates with adverse prognosis in glioblastoma and lower-grade gliomas, positioning it as a potential therapeutic target 4. These findings establish C1s as a central regulator of innate immunity with emerging roles in cancer biology and neuroinflammatory diseases.