Understanding podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy. Podocytes, essential for maintaining the glomerular filtration barrier, are vulnerable to immune-mediated injury, leading to proteinuria and chronic kidney disease (CKD). This review explores the mechanisms of podocyte immune injury in various diseases and recent advances in immunotherapy. Podocytes exhibit immune cell-like characteristics, participating in both innate and adaptive immunity. They play a critical role in mediating glomerular injury and are potential therapeutic targets. The review highlights the role of TLRs, NLRP3 inflammasome, and cGAS-STING pathways in podocyte innate immunity, as well as the involvement of adaptive immune responses, including T and B cells. The complement system also contributes to podocyte injury. Common proteinuric glomerular diseases, such as minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and lupus nephritis, are associated with immune-mediated podocyte injury. Therapeutic strategies targeting immunity in podocyte injury include immunosuppressive drugs like glucocorticoids, cyclophosphamide, and rituximab. Understanding these mechanisms is crucial for developing effective treatments for podocyte-related disorders.Understanding podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy. Podocytes, essential for maintaining the glomerular filtration barrier, are vulnerable to immune-mediated injury, leading to proteinuria and chronic kidney disease (CKD). This review explores the mechanisms of podocyte immune injury in various diseases and recent advances in immunotherapy. Podocytes exhibit immune cell-like characteristics, participating in both innate and adaptive immunity. They play a critical role in mediating glomerular injury and are potential therapeutic targets. The review highlights the role of TLRs, NLRP3 inflammasome, and cGAS-STING pathways in podocyte innate immunity, as well as the involvement of adaptive immune responses, including T and B cells. The complement system also contributes to podocyte injury. Common proteinuric glomerular diseases, such as minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and lupus nephritis, are associated with immune-mediated podocyte injury. Therapeutic strategies targeting immunity in podocyte injury include immunosuppressive drugs like glucocorticoids, cyclophosphamide, and rituximab. Understanding these mechanisms is crucial for developing effective treatments for podocyte-related disorders.