TNFSF11 and osteoporosis: 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)