Calcium-sensing receptor: a potential target for liver health and diseases

Calcium-sensing receptor (CaSR) plays a critical role in regulating extracellular calcium (Ca²⁺) concentrations and maintaining Ca²⁺ homeostasis. Emerging evidence reveals that CaSR is expressed in hepatic cells and tissues across multiple species, including humans, mice, and cattle, challenging the traditional view of the liver as a non-calciotropic organ. CaSR is also implicated in key hepatic processes such as lipid metabolism and bile secretion. Furthermore, CaSR significantly influences liver pathophysiology, contributing to the development and progression of pathological conditions such as hepatic ischemia-reperfusion injury, cholestasis, non-alcoholic fatty liver disease, liver cirrhosis, insulin resistance, and liver cancer. Recent studies have also highlighted CaSR's interactions with nutrient-sensing pathways and its role in immune regulation, positioning it as a promising therapeutic target for hepatic metabolic disorders and liver cancer. This review explores the multifaceted roles of CaSR in liver physiology and disease, emphasizing its potential as a novel therapeutic target for addressing hepatic physiology and pathology.