However, although the treatment of matrilin-3 mutant cells with exogenous MANF reduced the levels of GRP78, it did not reduce the levels of mutant matrilin-3 retention, indicating that it is the intracellular MANF that plays a beneficial role in the pathobiology of matrilin-3 related MED. This evidence concerns the gene HSPA5 and multiple epiphyseal dysplasia.