Human complement Factor H-related protein 1 (FHR-1) is one of complement Factor H-related proteins (FHRs) and plays an important role in innate immunity. In particular, FHR-1 promotes complement activation by competing with Factor H (FH) for ligands on different surfaces or directly binding to C3b and native C3. Paradoxically, FHR-1 restrains complement activation by inhibiting C5 convertase and terminal complement complex (TCC) formation, and in vitro assays showed that the physiological concentration of FHR-1 had no obvious C3 and C5 regulatory activity. FHR-1 also plays a role in the inflammatory process. MDA-bound FHR-1 promotes inflammatory cytokine release from monocytes in a complement-independent manner. However, its deficiency increases TNFα, IL1β, IL6, and IL10 secretion from monocytes stimulated with LPS and R484. These contradictory effects of FHR-1 in innate immunity indicate that FHR-1 may function differently in different scenarios. Dysregulation of innate immunity due to frequent CFHR1 variations is associated with various immune inflammatory disorders. Mutations in the C-terminus of FHR-1 that increase its similarity with FH are associated with atypical haemolytic uraemia syndrome (aHUS). In contrast, mutations in the N-terminus that increase the multimerization of FHRs are associated with C3 glomerulopathy (C3G). Changes in FHR-1 concentration have been observed in other diseases. The different functions of the C-terminus and N-terminus of FHR-1 and the distinct function of FHR-1 under various conditions may explain the association of CFHR1 variations with different diseases. Here, we summarized the recent progress on FHR-1 and dissected its role in various immune inflammatory disorders, helping to comprehend and further explore the disease pathogenesis.