Binding of LGR4 to RANKL has been shown to downregulate RANK in HEK293T cells, abrogating the RANK/RANKL interaction that controls differentiation of mature osteoclasts.(62, 63) These findings corroborate with evidence that, in humans, rare nonsense mutations of the LGR4 gene are linked with osteoporosis.(61, 64). This evidence concerns the gene LGR4 and osteoporosis.