Jph3, or junctophilin 3, is a gene whose protein product serves to stabilize junctional membrane complexes and regulate neuronal calcium flux [3]. It also participates in pathways related to cell proliferation, apoptosis, and insulin secretion. Its role in maintaining normal physiological functions makes it biologically important, and genetic models like knockout mice are valuable for studying its functions.

In cancer research, Jph3 has been shown to act as a tumor suppressor. In hepatocellular carcinoma (HCC), Jph3 is inactivated by promoter methylation, leading to poor survival outcomes. Demethylation or increasing its expression inhibits HCC cell proliferation, invasion, and migration [1]. Similar findings are seen in digestive cancers where Jph3 promoter CpG methylation is associated with tumor progression, and its expression promotes mitochondrial-mediated apoptosis [2].

In Huntington disease-like 2 (HDL2), Jph3 expression is decreased, and mice with partial or complete loss of Jph3 (Jph3 hemizygous and null mice) exhibit abnormal motor function, suggesting that loss of Jph3 contributes to HDL2 pathogenesis [3].

In pancreatic beta cells, knockdown of Jph3 in mice (si-Jph3) impairs glucose-stimulated insulin secretion, affecting mitochondrial function, calcium signaling, and ER-mitochondria contact [4].

In conclusion, Jph3 is crucial for multiple biological processes. Through model-based research, especially using gene knockout mouse models, it has been revealed that Jph3 plays significant roles in cancer development and neurodegenerative diseases like HDL2, as well as in insulin secretion regulation. Understanding Jph3's functions provides insights into disease mechanisms and potential therapeutic targets.