Glycosylation Heterogeneity of α1-Acid Glycoprotein: Disease-Associated Glycoform Remodeling, Regulatory Mechanisms, and Clinical Translation

α1-Acid glycoprotein (AGP) is a heavily glycosylated acute-phase protein whose N-linked glycan microheterogeneity plays an important regulatory role in pathophysiological processes. This review synthesizes decades of basic and clinical research, focusing on the five conserved N-glycosylation sites of AGP. Specifically, it summarizes disease-specific patterns of glycan remodeling in inflammation, cancer, and autoimmune diseases; discusses the molecular effects through which glycosylation modulates AGP conformation, receptor-binding properties, and downstream signaling pathways; examines disease-associated molecular fingerprints arising from site-specific glycosylation and their relationships with disease onset and progression; and highlights the translational potential of AGP glycosylation for early diagnosis, prognostic assessment, and targeted drug development. Current evidence indicates that most abnormalities in AGP glycosylation are associated with disease, whereas direct causal evidence for the involvement of glycosylation in disease progression remains incomplete. Important limitations also remain: the precise molecular mechanisms regulating AGP glycosylation under different pathological conditions have not been fully elucidated; experimental findings are inconsistent across cohorts and analytical platforms; and standardized analytical systems suitable for clinical application have yet to be established. By integrating the available evidence, this review provides a theoretical framework for advancing the translation of AGP glycosylation features into precision medicine.