Proposed model for the role of CaR in HSC lodgment in vivo. Active bone remodeling releases Ca²⁺ ions into the endosteal region of the BM. HSCs arriving at the endosteal region are able to sense the released Ca²⁺ ions through the CaR. When the CaR is activated by Ca²⁺ ions, CXCR4 signaling is activated, which is known to be involved in cell survival and the retention of HSCs in the BM. Furthermore, activation of the CaR also enhances HSC adhesion to major ECM components in the adult BM, such as collagen I. This complex interplay of intracellular signaling dictates the fate of the transplanted HSCs.