Hepatic stellate cells (HSCs) have been studied for over 130 years, but their role in liver injury and fibrosis was only clearly understood after improved methods for their isolation and characterization. HSCs are vital for liver function and response to injury, and their activation into contractile myofibroblasts is a key mechanism in hepatic fibrosis. However, HSCs have a broad range of functions beyond fibrosis, including liver development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Recent studies have shown that HSCs are essential for hepatic progenitor cell amplification and differentiation, and they exhibit remarkable plasticity in both their intermediate filament phenotype and functions. HSCs are central to a complex sinusoidal environment, requiring tightly regulated autocrine and paracrine signaling, rapid responses to extracellular matrix changes, and sensitivity to liver metabolic needs. They also play roles in systemic homeostasis, such as retinoid storage, antigen presentation, and interactions with bone marrow-derived cells. HSCs were first described by Kupffer in 1876, and their identity was later confirmed by Rothe in 1882. Over time, various names were used for HSCs, leading to a standardized name in 1996: hepatic stellate cell. HSCs are located in the subendothelial space, between hepatocytes and sinusoidal endothelial cells, and make up about one-third of the nonparenchymal cell population in normal liver. Their ultrastructure includes spindle-shaped cell bodies with oval or elongated nuclei, moderately developed rough endoplasmic reticulum, and prominent dendritic cytoplasmic processes. HSCs store vitamin A (retinoid) in cytoplasmic droplets, which exhibit blue-green autofluorescence when excited with light at 328 nm. These droplets vary in size and distribution depending on the cell's location and species. HSCs originate from either endoderm or the septum transversum, and their embryonic origin is still debated. In humans, HSCs appear in the second half of the third month of gestation, and in rats, they reach their final size after five weeks post-birth. HSCs express various markers, including desmin, α-SMA, and GFAP, and their heterogeneity and plasticity are evident in their varying cytoskeletal phenotypes and functions. HSCs can be activated into myofibroblasts during liver injury, leading to fibrosis, but they also play roles in liver development, regeneration, and immunoregulation. HSCs are also found in other organs, such as the pancreas, and share similarities with pancreatic stellate cells. HSCs are involved in fibrogenesis in various tissues, including the liver,Hepatic stellate cells (HSCs) have been studied for over 130 years, but their role in liver injury and fibrosis was only clearly understood after improved methods for their isolation and characterization. HSCs are vital for liver function and response to injury, and their activation into contractile myofibroblasts is a key mechanism in hepatic fibrosis. However, HSCs have a broad range of functions beyond fibrosis, including liver development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Recent studies have shown that HSCs are essential for hepatic progenitor cell amplification and differentiation, and they exhibit remarkable plasticity in both their intermediate filament phenotype and functions. HSCs are central to a complex sinusoidal environment, requiring tightly regulated autocrine and paracrine signaling, rapid responses to extracellular matrix changes, and sensitivity to liver metabolic needs. They also play roles in systemic homeostasis, such as retinoid storage, antigen presentation, and interactions with bone marrow-derived cells. HSCs were first described by Kupffer in 1876, and their identity was later confirmed by Rothe in 1882. Over time, various names were used for HSCs, leading to a standardized name in 1996: hepatic stellate cell. HSCs are located in the subendothelial space, between hepatocytes and sinusoidal endothelial cells, and make up about one-third of the nonparenchymal cell population in normal liver. Their ultrastructure includes spindle-shaped cell bodies with oval or elongated nuclei, moderately developed rough endoplasmic reticulum, and prominent dendritic cytoplasmic processes. HSCs store vitamin A (retinoid) in cytoplasmic droplets, which exhibit blue-green autofluorescence when excited with light at 328 nm. These droplets vary in size and distribution depending on the cell's location and species. HSCs originate from either endoderm or the septum transversum, and their embryonic origin is still debated. In humans, HSCs appear in the second half of the third month of gestation, and in rats, they reach their final size after five weeks post-birth. HSCs express various markers, including desmin, α-SMA, and GFAP, and their heterogeneity and plasticity are evident in their varying cytoskeletal phenotypes and functions. HSCs can be activated into myofibroblasts during liver injury, leading to fibrosis, but they also play roles in liver development, regeneration, and immunoregulation. HSCs are also found in other organs, such as the pancreas, and share similarities with pancreatic stellate cells. HSCs are involved in fibrogenesis in various tissues, including the liver,