C1R encodes a serine protease that serves as a critical catalytic component of the C1 complex, which initiates the classical pathway of complement. Upon binding of C1Q to antigen-antibody complexes on pathogen surfaces, C1R undergoes autocatalytic activation and subsequently cleaves and activates C1S, the second protease in this cascade, leading to complement-mediated phagocytosis and adaptive immune signaling. The gene exhibits an unusual intronless serine protease domain architecture compared to other vertebrate serine proteases 1, and C1R allelic variants have been characterized at five amino acid positions within domains encoding structural motifs 2. C1R deficiency is associated with Ehlers-Danlos syndrome, periodontal type, 1. Recent proteomic studies have identified elevated C1R in plasma extracellular vesicles as a potential biomarker in sarcopenia, where it achieved an area under the curve of 0.7476 in receiver operating characteristic analysis and would enable sarcopenia diagnosis with 75% sensitivity and 66.67% specificity 3. These findings suggest C1R may have broader roles in age-related musculoskeletal decline beyond its canonical complement function, though the mechanisms underlying this association remain to be clarified.