LIMA1, also known as EPLIN or SREBP3, is a LIM domain and actin-binding protein. It serves as a key regulator in multiple biological processes. In the context of lipid metabolism, it is crucial for intestinal cholesterol absorption, bridging NPC1L1 to a transportation complex containing myosin Vb [1]. It is also involved in cytoskeletal dynamics, cell motility, cell division, gene regulation, apical extrusion, angiogenesis, cellular metabolism and lipid metabolism [2].

In mouse models, Lima1-deficient mice display reduced cholesterol absorption and resistance to diet-induced hypercholesterolemia, indicating its role in regulating intestinal cholesterol absorption [1]. In lipotoxic hepatocytes, LIMA1-enriched small extracellular vesicles promote hepatic stellate cells activation via inhibiting mitophagy [3]. Also, LIMA1 O-GlcNAcylation promotes hepatic lipid deposition through inducing β-catenin-regulated FASn expression in metabolic dysfunction-associated steatotic liver disease [4].

In conclusion, Lima1 is an important protein with diverse functions. The study of Lima1 knockout mouse models has revealed its significance in lipid-related diseases such as hypercholesterolemia and metabolic dysfunction-associated steatotic liver disease, providing insights into the underlying molecular mechanisms and potential therapeutic targets.