This review summarizes recent progress in natural and engineered structural modifications of IgG antibodies, including allotypic variation, glycosylation, Fc engineering, and Fc gamma receptor (FcγR) binding optimization. The functional consequences of these modifications are discussed to highlight their potential for therapeutic applications. IgG antibodies are critical components of the adaptive immune system, binding to and neutralizing pathogens. Structural modifications can enhance their therapeutic potential by influencing effector functions such as complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), and phagocytosis. The five major classes of Ig in humans are IgG (70-85%), IgA (5-15%), IgM (5-10%), with trace amounts of IgD (≈0.25%) and IgE (<0.25%). IgG can be divided into four subclasses: IgG1 (60-70%), IgG2 (20-30%), IgG3 (5-8%), and IgG4 (1-3%). IgG1 and IgG3 are more potent in inducing effector functions, while IgG2 and IgG4 are less so. Structural modifications such as allotypic variation, glycosylation, and Fc engineering can influence the binding of IgG to FcγRs, FcRn, and complement. These modifications can affect the half-life, stability, and effector functions of IgG. For example, IgG4 has a shorter half-life and lower affinity for FcγRs and C1q compared to other subclasses. However, IgG4 can still be pathogenic in certain conditions, such as pemphigus or IgG4-related disease. Glycosylation of IgG, particularly at the N297 site, significantly impacts its binding to FcγRs and complement. Afucosylated IgG has higher affinity for FcγRIIIa and enhances ADCC. However, hypergalactosylation of afucosylated IgG1 can further increase FcγRIIIa affinity. Sialylation of IgG can reduce ADCC, while galactosylation can enhance C1q binding and complement activity. Engineering mutations can modulate FcγR binding, with some mutations enhancing or reducing binding to different FcγR subtypes. For example, mutations such as G236A, S239D/I332E, and D270A can increase or decrease binding to FcγRs. The LALA mutation (L234A/L235A) reduces binding to FcγRs and is used in therapeutic antibodies. The LALA-PG mutation (LALA combined with P331S) eliminates FcγR binding without disrupting the overall conformation of the Fc region. These structuralThis review summarizes recent progress in natural and engineered structural modifications of IgG antibodies, including allotypic variation, glycosylation, Fc engineering, and Fc gamma receptor (FcγR) binding optimization. The functional consequences of these modifications are discussed to highlight their potential for therapeutic applications. IgG antibodies are critical components of the adaptive immune system, binding to and neutralizing pathogens. Structural modifications can enhance their therapeutic potential by influencing effector functions such as complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), and phagocytosis. The five major classes of Ig in humans are IgG (70-85%), IgA (5-15%), IgM (5-10%), with trace amounts of IgD (≈0.25%) and IgE (<0.25%). IgG can be divided into four subclasses: IgG1 (60-70%), IgG2 (20-30%), IgG3 (5-8%), and IgG4 (1-3%). IgG1 and IgG3 are more potent in inducing effector functions, while IgG2 and IgG4 are less so. Structural modifications such as allotypic variation, glycosylation, and Fc engineering can influence the binding of IgG to FcγRs, FcRn, and complement. These modifications can affect the half-life, stability, and effector functions of IgG. For example, IgG4 has a shorter half-life and lower affinity for FcγRs and C1q compared to other subclasses. However, IgG4 can still be pathogenic in certain conditions, such as pemphigus or IgG4-related disease. Glycosylation of IgG, particularly at the N297 site, significantly impacts its binding to FcγRs and complement. Afucosylated IgG has higher affinity for FcγRIIIa and enhances ADCC. However, hypergalactosylation of afucosylated IgG1 can further increase FcγRIIIa affinity. Sialylation of IgG can reduce ADCC, while galactosylation can enhance C1q binding and complement activity. Engineering mutations can modulate FcγR binding, with some mutations enhancing or reducing binding to different FcγR subtypes. For example, mutations such as G236A, S239D/I332E, and D270A can increase or decrease binding to FcγRs. The LALA mutation (L234A/L235A) reduces binding to FcγRs and is used in therapeutic antibodies. The LALA-PG mutation (LALA combined with P331S) eliminates FcγR binding without disrupting the overall conformation of the Fc region. These structural