In its native soluble form, the human protein β2-microglobulin (β2m) has a classical immunoglobulin fold and forms the non-covalently bound light chain of the class 1 major histocompatibility complex. During its normal catabolic cycle, β2m is degraded by the kidney. In patients with renal failure, the concentration of β2m in serum is increased by up to 60-fold, whereupon the full-length disulfide bonded protein self-associates into amyloid fibrils that accumulate in the musculo-skeletal system, causing dialysis-related amyloidosis.21 Like other soluble globular proteins involved in amyloidosis, native β2m is stable as a monomer in solution, and partial or full unfolding is required to initiate assembly into amyloid fibrils in vitro.22 While amyloid formation at neutral pH is a slow and inefficient process, seeding and/or addition of copper ions, detergents, or organic co-solvents can induce fibril formation at neutral pH.23–25 Under highly acidic conditions, the precursor monomeric protein is unfolded,26 and amyloid fibrils are rapidly formed in a nucleation-dependent mechanism.27,28 These fibrils display all the hallmarks of authentic amyloid, including nucleation-dependent polymerisation kinetics, Congo red birefringence, a cross-β fibre diffraction pattern, and the ability to bind serum amyloid P component, apolipoprotein E, glycosaminoglycans, and the generic anti-amyloid antibody WO1.24,27,29 They also show the same characteristic amide I band in FTIR spectra as fibrils formed in vitro at neutral pH, as well as those extracted from patient tissues, confirming their structural authenticity.30 FTIR analysis indicates a high β-sheet content in the fibrils, most likely involving a predominantly parallel arrangement of β-strands, in contrast with the anti-parallel arrangement of β-strands in the immunoglobulin fold of the native monomer.31