Factor H-related protein 1 (FHR-1) is a member of the factor H protein family, which is involved in regulating innate immune complement reactions. Genetic modification of the encoding gene, CFHR1 on human chromosome 1, is involved in diseases such as age-related macular degeneration, C3glomerulopathy, and atypical hemolytic uremic syndrome, indicating an important role for FHR-1 in human health. Recent research data demonstrate that FHR-1 levels increase in IgA nephropathy and ANCA vasculitis and that FHR-1 induces strong inflammation in monocytes on necrotic-type surfaces, suggesting a complement-independent role. These new results increase our knowledge about the role of this complement protein in pathology and provide a new therapeutic target, particularly in the context of inflammatory diseases induced by necrosis. This review summarizes current knowledge about FHR-1 and discusses its role in complement reactions and inflammation. Abbreviations: FHR-1, factor H-related protein 1; IgAN, IgA associated nephropathy or Berger's disease; AMD, age-related macular degeneration; C3G complement C3 glomerulopathy; aHUS, atypical hemolytic uremic syndrome; CFH, complement factor H gene, SCR, short consensus repeat; RCA, regulator of complement activation; SLE, systemic lupus erythematosus; TCC, terminal complement complex; CRP, C-reactive protein. unclear function. Recent studies report different regulatory roles for FHR-1, both as an inhibitor of terminal complement pathway activation and as an inducer of complement by out-competing the inhibitor factor H for binding to C3b, as well as by inducing NLRP3 in monocytes. The two faces of FHR-1 suggest that the protein may act in a certain plasma concentration together with factor H to regulate complement on healthy surfaces, but that when FHR-1 concentrations increase it may also act as a deregulator and inducer of inflammation on necrotic-type surfaces. Further studies will reveal more information about the plasticity of this protein.