CD81, a tetraspanin protein, participates in diverse cellular processes such as membrane organization, protein trafficking, cellular fusion, and cell-cell interactions. In the immune system, it regulates immune synapse, receptor clustering, and signaling, and mediates immune suppression. It is also a key player in pathogen entry, like hepatitis C virus into hepatocytes [2,3,5].

CD81-deficient mouse models have shown that CD81 loss causes diet-induced obesity, insulin resistance, and adipose tissue inflammation. It controls beige adipocyte progenitor cell growth and energy balance via FAK signaling, as CD81 forms a complex with integrins and mediates integrin-FAK signaling in response to irisin [1]. In Herpes simplex virus 1 (HSV-1) infection, CD81 KO neuroblastoma cells had impaired viral DNA replication and greatly diminished viral titers, though there were no defects in viral entry or early protein marker expression [4].

In conclusion, CD81 is crucial in multiple biological processes and disease conditions. Model-based research, especially through KO mouse models, has revealed its significance in energy homeostasis and pathogen-host interactions. Understanding CD81's functions may offer new strategies for treating obesity-related metabolic disorders and viral infections.