Immunoglobulin light chain (misfolded form)

Misfolded immunoglobulin light chain refers to the light chain component of antibodies that, due to a clonal plasma cell disorder, is overproduced, secreted as a free (unbound) protein, and becomes prone to misfolding. This misfolding promotes aggregation into insoluble amyloid fibrils, which deposit in organs and tissues, leading to AL amyloidosis. The process is driven by both inherited and somatic mutations in the light chain gene sequence that destabilize the native fold and enhance amyloidogenic potential. The resulting amyloid deposits cause progressive organ dysfunction, frequently affecting the heart and kidneys, and can be fatal if not managed. Therapeutic interventions aim at eliminating the abnormal plasma cell clone, reducing light chain production, and, more recently, stabilizing the native structure of the light chain to prevent misfolding.

Other names

Misfolded immunoglobulin light chainAmyloidogenic light chainAL proteinLight chain amyloidBence Jones protein (misfolded/amyloidogenic context)

Inhibit plasma cell proliferation and light chain production (chemotherapies, immunomodulators, proteasome inhibitors, monoclonal antibodies); Stabilize native light chain conformation to prevent misfolding/aggregation (kinetic stabilizers under investigation).