Following glomerular ultrafiltration, immunoglobulin light chains (LCs) bind to a receptor on the apical surface of proximal tubule epithelial cells and undergo endocytosis. Through a process not yet understood, NF-κB and the MAP kinase pathways are activated, resulting in production of chemokines and cytokines that include IL-6, IL-8, MCP-1, and TNF-α. Local production of these chemoattractants results in renal interstitial inflammation, TGF-β activation, and matrix protein production by fibroblasts. In the distal nephron, LC coprecipitates with Tamm-Horsfall protein (THP) to produce an intraluminal cast that obstructs tubule fluid flow and produces breaks in the epithelial cell lining, compounding the interstitial scarring. PACAP38 prevents the activation of the proximal tubule epithelium by LC and inhibits production of TNF-α and IL-6. Illustration by A. Y. Chen.