Chrm3, encoding the muscarinic acetylcholine receptor M3, is a key gene involved in multiple physiological processes. The M3 receptor is one of the well-characterized receptors of pancreatic β cells and is known to regulate insulin secretion. It is also associated with various signaling pathways, such as those related to calcium regulation [3,4,5].

In disease-related studies, in a severe acute pancreatitis mice model, Chrm3 was upregulated in pancreatitis. Reduction of Chrm3 decreased the pathological lesion of severe acute pancreatitis and reduced amylase activities in serum, suggesting that Chrm3 can suppress acinar cells necrosis, at least in part by stabilizing caspase-8 [3]. In addition, in L-arginine-induced severe acute pancreatitis, CHRM3 activation was found to promote necrosis through the MAPK-p38/miR-31-5p/RIP3 axis [5].

In glioblastoma, high levels of CHRM3 correlated with poor prognosis. Knockdown of CHRM3 inhibited GBM cell growth and invasion, and suppression of CHRM3 in an orthotopic GBM animal model significantly prolonged survival time [2].

In colon cancer, the proliferative effects of bile acids on colon epithelium are through interaction with muscarinic-3 receptors, and CHRM3-associated miRNAs might play a role in bile acid-induced proliferation of H508 colon cancer cells [1].

In castration-resistant prostate cancer, CHRM3-mediated focal adhesion kinase/YES-associated protein (YAP) signalling is essential for cell growth, and miR-15b-5p can inhibit this growth by targeting CHRM3 [6].

In conclusion, Chrm3 plays diverse and crucial roles in various biological processes and disease conditions. Gene-knockout and other loss-of-function experiments, especially in mouse models, have been instrumental in revealing its functions in diseases like pancreatitis, glioblastoma, colon cancer, and prostate cancer. Understanding the role of Chrm3 provides insights into disease mechanisms and potential therapeutic targets.