According to the model, the level of renal function is the main determinant of plasma β2M concentrations by affecting both removal (glomerular filtration) and generation of free β2M. Interference with the binding of β2M to MHC and non-classical MHC molecules [possibly in the endosomes where these interactions are initiated (310, 311)] by other uremic retention solutes constitutes a major source for the heightened generation of β2M in uremia. The gene discussed is B2M; the disease is uremia.