Chrnb4, encoding the neuronal acetylcholine receptor subunit beta-4, is part of the ligand-gated ion channels family known as neuronal nicotinic acetylcholine receptors (nAChRs). These receptors are allosterically regulated and play a role in various biological processes, especially those related to the nervous system. The CHRNA5-CHRNA3-CHRNB4 gene cluster is associated with nicotine addiction, as genetic variation in this cluster increases vulnerability to tobacco dependence and smoking-associated diseases [1].

In mouse models, conditional knockout of Dicer1 using Chrnb4-Cre leads to cone cell death and impaired photopic vision, suggesting that Chrnb4-expressing cone cells rely on Dicer1 for survival and normal function [3].

In human diseases, high expression of CHRNB4 is associated with unfavorable prognosis in esophageal squamous cell carcinoma (ESCC) and head-and-neck squamous cell carcinoma (HNSC). Knockdown of CHRNB4 can inhibit the proliferation of ESCC cells via the Akt/mTOR and ERK1/2/mTOR pathways [2]. Also, in non-small cell lung cancer, unmethylation of the CHRNB4 gene is an unfavorable prognostic factor, associated with upregulation of its mRNA expression [4].

In conclusion, Chrnb4 is crucial for the normal function of cone photoreceptor cells as demonstrated by conditional knockout mouse models. In addition, its dysregulation is implicated in several human cancers, highlighting its potential as a biomarker and therapeutic target in these disease areas.