Lysosomal checkpoints in renal autoimmunity: from antigen processing to metabolic-immune crosstalk

Lysosomes serve as critical intracellular hubs for degradation and signaling, playing a central role in maintaining immune homeostasis. In recent years, lysosomal functions have been conceptualized as a series of "checkpoints" that finely regulate the initiation and progression of autoimmune kidney diseases. This review systematically examines the multifaceted roles of lysosomal checkpoints in renal autoimmunity, with a focus on their mechanisms in autoantigen processing and presentation, immune cell activation and breakdown of tolerance, and the emerging area of metabolic-immune crosstalk. By integrating the latest research, this article aims to elucidate the potential of targeting lysosomal pathways as a novel therapeutic strategy for autoimmune kidney diseases such as lupus nephritis and ANCA-associated vasculitis.