Ehbp1, also known as EH domain-binding protein 1, is an adaptor protein with diverse functions. It plays roles in regulating vesicular trafficking by recruiting Rab8 family members and Eps15-homology domain-containing proteins 1/2 (EHD1/2), and links endosomes to the actin cytoskeleton [4]. It is associated with pathways related to cholesterol metabolism, Wnt/Wingless signaling, and polarized transport of membrane proteins, and is important for normal development and tissue homeostasis [1,2,3]. Genetic models, such as knockout mouse models, are valuable for studying its functions.

In metabolic dysfunction-associated steatohepatitis (MASH), human fibrotic livers have decreased Ehbp1 levels. In mouse models, Ehbp1 loss-of-function increases MASH fibrosis, while gain-of-function decreases it. Mechanistically, Ehbp1 promotes sortilin-mediated PCSK9 secretion, leading to LDL receptor degradation, decreased LDL uptake, and reduced TAZ (a fibrogenic effector). Ehbp1 deficiency also affects the intracellular localization of retromer, which is required for sortilin stabilization [1].

In conclusion, Ehbp1 is essential for multiple biological processes. Its role in cholesterol metabolism and MASH fibrosis, as revealed by mouse models, highlights its importance in liver-related diseases. Understanding Ehbp1 can potentially provide insights into the mechanisms of MASH and offer new strategies for its treatment.