A small plasma cell clone produces poor quality amyloidogenic light chains that, mostly outside the plasma cell, tend to misfold and form amyloid fibrils (A). Inside the plasma cell the increased protein load induces ER stress and mechanisms to retain homeostasis require the rapid clearance of these proteins. The degradation of these poor quality proteins is largely dependent on proteasome activity. Bortezomib blocks proteasome degradation of proteins and increases poor quality protein load within ER thus inducing ER stress beyond the capacity of the control mechanisms and resulting in plasma cell apoptosis (B).