Secretory and membrane proteins normally fold and assemble in the endoplasmic reticulum (ER) before moving to the Golgi. Mutant proteins that fail to fold properly are mainly dispatched to the cytoplasm for degradation but some get stuck in the ER and cause ER storage diseases. On p. 2532, Roberto Sitia and co-authors provide new insights into these diseases by investigating the biogenesis of Russell bodies, dilated ER cisternae containing mutant immunoglobulins that are often seen in multiple myeloma. The authors show that immunoglobulin-μ heavy chains that lack the first constant domain (μΔCH1) accumulate as detergent-insoluble aggregates in Russell bodies when their synthesis rate exceeds their degradation rate. Where μΔCH1 chains aggregate, however, depends on the proteins they interact with. If immunoglobulin light chains are present, they condense in large ribosome-coated structures; in their absence, they aggregate in smooth tubular vesicles with ERGIC-53, a marker of the ER-Golgi intermediate compartment (ERGIC). These results reveal a new role for ERGIC-53 and indicate that a disruption of the equilibrium between synthesis, processing and degradation of aberrant proteins causes ER storage diseases.