AL amyloidosis is caused by a small or modest, relatively indolent, plasma cell clone secreting light chains (ratio of λ to κ light chains, 4:1) with abnormal folding (misfolded) caused by mutations (symbolized by red dot) that affect critical structural sites. These light chains are prone to aggregation, form amyloid fibrils, and become toxic for cells and tissues, producing failure of vital organs. Heart involvement is the most clinically relevant because it is the cause of death in virtually all patients. Inset: Survival of 1131 patients with AL amyloidosis according to the year of diagnosis followed at the Pavia Amyloid Research and Treatment Center. Although survival continues to improve, the slope of the first part of the curves has not changed during almost 30 years, mostly because of early death of patients with severe cardiac involvement. ANS indicates autonomous nervous system; CHF, congestive heart failure defined as New York Heart Association class III or IV; GI, gastrointestinal tract; and PNS, peripheral nervous system. Professional illustration by Kenneth X. Probst.