Proteins of the Factor H protein family bind to C reactive protein and regulate complement activity on apoptotic and necrotic host cells The complement system protects the host against foreign organisms and induces a non inflammatory phagocytosis of damaged or mutated host cells. Complement regulators protect intact host cells against complement attack and prevent inflammatory reactions. Factor H is the main soluble regulator of the alternative complement pathway. Factor H binds to host cells and blocks the alternative complement activation to prevent cell and tissue damages. In addition Factor H binds the acute phase protein C reactive protein (CRP). CRP opsonizes apoptotic and necrotic host cells and microbial invaders for phagocytosis by activating the classical complement cascade. However the amplification loop via the alternative pathway and the pro inflammatory terminal complement pathway are inhibited. Here I analyzed the role of Factor H binding to CRP in this limitation of complement. Furthermore the Factor H related (CFHR) proteins CFHR 1 CFHR 4A and CFHR 4B which have a high similarity to Factor H were functionally characterized. In this work I show that Factor H CFHR 4A and CFHR 4B bind different isoforms of CRP. Factor H binds monomeric CRP (mCRP) while CFHR 4A 4B bind pentameric CRP (pCRP). Moreover the analyzed proteins of the Factor H protein family regulate complement at the surface of cellular debris. Factor H and CFHR 1 inhibit complement and protect cellular debris from inflammatory complement attack while CFHR 4A 4B enhance the cell opsonization through recruitment of pCRP.