Erbin, short for Erbb2 interacting protein, belongs to the leucine-rich repeat and PDZ domain (LAP) family. It acts as an adaptor protein, targeting the basolateral localization of the Her2 receptor by directly binding to its C-terminus. Erbin can inhibit multiple signaling pathways such as Ras-mediated activation of the mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB) and transforming growth factor β (TGF-β) signaling pathways, suggesting its significance in maintaining normal cellular functions [5].

In various disease-related studies, Erbin knockout (KO) mouse models have provided valuable insights. In platelets/megakaryocytes, Erbin KO suppressed lung metastasis in mice, promoted platelet aggregations, and enhanced mitochondrial oxidative phosphorylation in B cells, which in turn promoted B cell-mediated antitumor immunity [1]. In B cells, Erbin deletion suppressed lung metastasis of colorectal cancer in vivo, as it enhanced the killing effects of CD8+ T cells on tumor cells by attenuating TGFβ-mediated suppression of migration of CXCR5+ IgA+ cells and STAT6-mediated PD1 expression [4]. In sepsis-related studies, Erbin KO in mice led to more pronounced neuronal damage and cognitive impairment in sepsis-associated encephalopathy, as it promoted microglial pyroptosis and inflammatory cytokines secretion [2]. In sepsis-induced cardiomyopathy, Erbin deficiency aggravated necroptosis, inflammation and systolic dysfunction, while overexpression of Erbin alleviated these symptoms by activating the PKA/CREB pathway [3]. In addition, Erbin KO in amygdala parvalbumin-positive neurons impaired excitatory postsynaptic responses and increased anxiety-like behaviors in mice [6].

In conclusion, model-based research, especially through Erbin KO mouse models, has revealed that Erbin plays crucial roles in multiple biological processes and disease conditions. It is involved in regulating tumor metastasis, immunity, neuroinflammation, cardiomyopathy, and anxiety-related behaviors. These findings provide potential therapeutic targets for treating related diseases.