Agrn, or agrin, is a protein-coding gene that plays a crucial role at the neuromuscular junction (NMJ). It is involved in the development and maintenance of the NMJ through regulating neural Agrn expression and downstream muscle LRP4-MuSK signaling [5]. It may also be associated with some "hallmark of aging" pathways related to the NMJ and neurons [6]. Genetic models, such as gene knockout (KO) mouse models, are valuable for studying its functions.

Mutations in Agrn can lead to congenital myasthenia syndromes (CMS), which are characterized by ptosis, muscle weakness, and motor development retardation. Early age of onset and lower-limb muscle weakness are common features of Agrn-related CMS, and these respond favorably to ephedrine treatment [1]. In breast cancer, suppression of Agrn enhances CD8+ T cell recruitment and inhibits cancer progression, with Agrn upregulation being positively correlated with clinicopathological stage and negatively with prognosis [2]. In lung adenocarcinoma, Agrn promotes cancer cell proliferation, migration, invasion, EMT, and tumorigenesis by activating the Notch signaling pathway, and anti-Agrn antibody treatment can inhibit tumor cell proliferation and promote apoptosis [3]. Null variants in Agrn can cause lethal fetal akinesia deformation sequence, indicating a strong genotype-phenotype correlation [4].

In conclusion, Agrn is essential for the normal function of the neuromuscular junction. Research using KO or other genetic models has revealed its significant roles in diseases such as CMS, breast cancer, lung adenocarcinoma, and lethal fetal akinesia deformation sequence. Understanding Agrn's functions provides insights into the mechanisms of these diseases and potential therapeutic targets.