Targeting annexin A1 in kidney diseases: a novel therapeutic avenue

Annexin A1 (ANXA1) is a critical effector of glucocorticoid-mediated anti-inflammatory responses and a regulator of lipid metabolism. Unlike conventional inflammatory markers, ANXA1 actively promotes the resolution of inflammation and preserves metabolic homeostasis through distinct molecular pathways. This review provides a mechanism-specific analysis of ANXA1 in kidney diseases. Structurally, ANXA1 consists of a unique N-terminal domain and a conserved C-terminal core that enables calcium-dependent membrane binding. Functionally, ANXA1 integrates proresolving signals primarily by activating formyl peptide receptor 2 (FPR2), which in turn suppresses NF-κB/NLRP3-driven inflammation and restores lipid homeostasis via the AMPK/PPARα pathway. These dual actions position ANXA1 as a key regulator linking inflammation and lipid metabolism in the kidney. We further evaluate current ANXA1-based agonists and inhibitors, linking molecular mechanisms to therapeutic potential. By integrating mechanistic insights with translational perspectives, this review identifies ANXA1 as a promising and druggable target for kidney diseases. Finally, we discuss major opportunities and challenges in translating ANXA1-targeted strategies into clinical practice for patients with kidney diseases.