Qianqian Yang, Yundong Xu, Jian Zhang, Niqin Xiao, Hongting Lu, Bingbing Chen, Bo Yang, Zhaohu Xie, Zhaofu Li
Uric acid has complex bidirectional effects on human physiology and disease, influenced by its antioxidant capacity, metabolic regulatory roles, and pro-inflammatory properties, all of which are highly context-dependent. In this review, we synthesize recent advancements related to the continuum from soluble uric acid (SUA) to amorphous monosodium urate (AMSU) and, ultimately, to crystalline monosodium urate (MSU). We propose that AMSU may act as a transitional intermediate that connects the soluble and crystalline states. Notably, AMSU may serve as a buffering stage between crystallization and inflammatory activation, providing a conceptual bridge between urate phase transitions and immune-metabolic signaling. Building on this idea, we establish a framework that links urate state dynamics with immune-metabolic pathways and disease progression. We systematically summarize the physiological roles of SUA in maintaining redox homeostasis and regulating metabolism, and we examine how sustained hyperuricemia contributes to chronic organ damage through impaired autophagy and metabolic inflammation. Additionally, we outline how the formation of MSU crystals triggers acute inflammatory responses via the TLR-NLRP3 two-signal model. Subsequent processes, such as neutrophil extracellular traps formation and macrophage polarization, drive chronic tissue remodeling and progressive pathology. Finally, we connect these mechanistic insights to both established and emerging therapeutic strategies, emphasizing the potential value of stage-specific and mechanism-oriented interventions. By conceptualizing uric acid biology as a dynamic, multi-state process, this review offers an integrated perspective on hyperuricemia-associated diseases and suggests directions for future targeted therapeutic research.