Abstract
Nonalcoholic fatty liver disease (NAFLD) is a prevalent and complex condition that affects millions of people globally. It occurs when fat, primarily triglycerides, accumulates in liver cells, leading to inflammation and damage. Calcium, an essential mineral, is involved in various physiological processes, including the regeneration process following liver injury. The endoplasmic reticulum (ER), a complex organelle involved in protein synthesis and lipid metabolism, regulates intracellular calcium levels. Dysregulation of this process can lead to calcium overload, oxidative stress, and cellular damage, all of which are hallmarks of NAFLD. Inositol 1,4,5-trisphosphate receptor (IP3R), a type of calcium ion channel, is found throughout the body, including the liver. IP3R is classified into three subtypes: IP3R1, IP3R2, and IP3R3, and it plays a critical role in regulating intracellular calcium levels. However, excessive calcium accumulation in the mitochondria due to an overload of calcium ions or increased IP3R activity can lead to NAFLD. Therefore, targeting calcium channels in the ER membrane may represent a promising therapeutic strategy for preventing and treating this increasingly prevalent metabolic disorder. It may help prevent mitochondrial calcium accumulation and reduce the risk of hepatic damage. This review article aimed to review the relationship between IP3R modulation and the pathogenicity of NAFLD, providing valuable insights to help researchers develop more effective treatments for the condition.