Frequent expression of an internally deleted LRP5 has been identified in parathyroid and breast cancers. Expression of the internally deleted LRP5 protein results in elevated levels of the active, unphosphorylated beta-catenin, enhanced expression of the both WNT-dependent reporter genes and the endogenous WNT-target gene MYC, and is required for cellular proliferation (Bjorklund et al, 2007a, b; Bjorklund et al, 2009). The in-frame internal deletion, which removes residues 666-809, arises through the aberrant use of cryptic splice sites in imperfect direct repeat sequences in exons 9 and 11 (Bjorklund et al, 2007b). This region has been shown to contain residues required for inhibition of beta-catenin activity by the negative regulator DKK1; consistent with this, expression of LRP5del666-809 is insensitive to inhibition by DKK1 (Zhang et al, 2004; Bjorklund et al, 2007b; Bjorklund et al, 2009). It has not been determined whether the LRP666-809del affects the interaction with SOST.