AL amyloidosis is a severe complication of plasma-cell disorders, secondary to monoclonal immunoglobulin light chain (LC) deposition in the kidney and other organs. Though the physicochemical properties of amyloid-forming monoclonal LCs have been demonstrated to be involved in their propensity to aggregate, it remains unclear where, when, and finally why amyloid fibrils are formed in vivo. Teng et al. shed light on this long-standing issue thanks to a new animal model.