Simultaneous stimulation of LGR4-positive HMCLs with Wnt ligand and R-spondin resulted in a major increase in LRP6 phosphorylation, β-catenin stabilization and translocation to the nucleus, activation of a Wnt reporter construct and an increase in MM cell proliferation, while the LGR4-negative HMCL L363 did not show this. Here, LGR4 is linked to Miyoshi myopathy.