CD64 is part of the immunoglobulin superfamily and plays a pivotal role in connecting humoral and cellular immunity. The extracellular domain of CD64 contains three immunoglobulin-like domains that readily bind to monomeric IgG. It has a higher affinity for IgG compared to CD32 (FcγRII) and CD16 (FcγRIII), and it shows different binding strengths to various IgG subclasses, with the order of affinity being IgG1/IgG3 > IgG4 > IgG2. CD64 is regulated by cytokines and is involved in the clearance of pathogens through antibody-dependent cellular cytotoxicity, phagocytosis, and immune complex removal. In the context of infectious diseases, CD64 has demonstrated high sensitivity and specificity in diagnosing such conditions compared to other markers like white blood cell count, C-reactive protein (CRP), and procalcitonin (PCT). It can be particularly useful in diagnosing bacterial infections, with sensitivity and specificity rates exceeding 90%. Moreover, the CD64 index has been found to correlate with the severity of sepsis and organ failure, making it a potential early predictor of mortality in sepsis patients.