Multiple therapeutic agents that target the complement system are currently investigated in various autoimmune and inflammatory disorders: (i) Regarding autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus, vasculitides, Sjögren’s syndrome, and systemic sclerosis evidence revealed that dysregulated complement activation is involved in the pathogenesis, particularly C3, C5aR, CR2, and MAC. The gene discussed is C5AR1; the disease is systemic sclerosis.