{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCalbindin‐D9k is a small cytosolic protein containing EF‐hand motifs that plays a pivotal role in the regulation of intracellular calcium levels in reproductive tissues. In the uterus, its expression is tightly controlled by steroid hormones – notably estrogen and progesterone – which together promote endometrial receptivity and support embryo implantation. Hormonal modulation leads to dynamic changes in calbindin‐D9k levels that, in turn, contribute to proper uterine function and successful reproductive outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its uterine functions, calbindin‐D9k is a key mediator of active calcium transport in the intestine, kidney, and placenta, and thus is central to systemic calcium homeostasis. Under normal conditions, compensatory mechanisms – including the expression of related calcium transporters such as TRPV channels, NCX1, and plasma membrane Ca²⁺‐ATPases – help maintain calcium balance. However, challenges such as dietary calcium or vitamin D deficiency, glucocorticoid treatment, or genetic ablation can disrupt this balance. In these contexts, experimental studies show that altered calbindin‐D9k expression impairs calcium re‐absorption and transcellular as well as paracellular transport pathways, ultimately affecting serum calcium levels and bone integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its well‐established roles in calcium buffering and transport, calbindin‐D9k also contributes to the regulation of cellular stress responses and survival. Structural analyses indicate that calcium binding induces conformational changes that may affect its interaction with other cellular targets. In pancreatic β‐cells, for example, calbindin‐D9k helps mitigate endoplasmic reticulum stress and apoptosis, thereby supporting insulin secretion and glucose homeostasis. Emerging evidence even suggests potential roles in neuronal development and function, highlighting the multifaceted nature of this protein in maintaining cellular calcium equilibrium under both physiological and pathological conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kun-Yeong Lee, Goo Taeg Oh, Joo-Hyoung Kang, et al. 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