EphB2, an erythropoietin-producing hepatocellular carcinoma (Eph) receptor, is a key component of the cell-cell communication system. It is involved in bidirectional signaling and is associated with multiple pathways, playing a vital role in various biological processes. EphB2 has been linked to the regulation of cell adhesion, migration, and synaptic plasticity, with its study often facilitated by genetic models like knockout (KO) mouse models [1,5].

In the context of diseases, EphB2 has diverse effects. In non-alcoholic steatohepatitis (NASH), EphB2-expressing hepatocytes, acting as a downstream effector of Notch signaling, contribute to disease progression, and knockdown of Ephb2 in hepatocytes ameliorates inflammation and fibrosis [2]. In hepatocellular carcinoma, EphB2 expression increases from normal to fibrotic to cancerous tissue, and endogenous EphB2 knockout attenuates tumor development. It also enhances cancer stem cell properties and sorafenib resistance by regulating the SRC/AKT/GSK3β/β-catenin signaling cascade [3]. In systemic sclerosis, EphB2 is up-regulated in skin tissue, and EphB2-knockout mice show reduced dermal fibrosis, indicating its role in promoting fibrosis [4]. In social isolation-induced memory forgetting, down-regulation of EphB2 in the hippocampal CA1 region mediates memory deficits, and viral-mediated EphB2 knockdown mimics these defects while restoration reverses them [5].

In conclusion, EphB2 is crucial for normal biological functions related to cell communication, adhesion, and synaptic plasticity. Through KO mouse models, its role in diseases such as NASH, hepatocellular carcinoma, systemic sclerosis, and social isolation-induced memory forgetting has been revealed. Understanding EphB2's functions provides potential therapeutic targets for these diseases.