This review discusses the impact of structural modifications on the effector functions of immunoglobulin G (IgG) antibodies. IgG antibodies, a critical component of the adaptive immune system, can be modified naturally or through engineered changes to enhance their therapeutic potential. The review covers allotypic variation, glycosylation, Fc engineering, and Fc gamma receptor (FcγR) binding optimization. Natural variations in IgG subclasses, such as IgG1 and IgG3, are more potent in inducing effector functions compared to IgG2 and IgG4. Engineered modifications, including mutations that affect hexamerization and complement binding, have been developed to enhance or reduce interactions with complement, FcγRs, and the neonatal Fc receptor (FcRn). The review also discusses the impact of these modifications on downstream effector functions, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Additionally, it explores the role of glycosylation, particularly at position 297 in the C1q2 domain, in binding to FcγRs and complement. The review highlights the potential of these modifications for therapeutic applications, including the development of novel antibody-based therapeutics and vaccines.This review discusses the impact of structural modifications on the effector functions of immunoglobulin G (IgG) antibodies. IgG antibodies, a critical component of the adaptive immune system, can be modified naturally or through engineered changes to enhance their therapeutic potential. The review covers allotypic variation, glycosylation, Fc engineering, and Fc gamma receptor (FcγR) binding optimization. Natural variations in IgG subclasses, such as IgG1 and IgG3, are more potent in inducing effector functions compared to IgG2 and IgG4. Engineered modifications, including mutations that affect hexamerization and complement binding, have been developed to enhance or reduce interactions with complement, FcγRs, and the neonatal Fc receptor (FcRn). The review also discusses the impact of these modifications on downstream effector functions, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Additionally, it explores the role of glycosylation, particularly at position 297 in the C1q2 domain, in binding to FcγRs and complement. The review highlights the potential of these modifications for therapeutic applications, including the development of novel antibody-based therapeutics and vaccines.