KCNJ15 encodes Kir4.2, an inwardly rectifying potassium channel that facilitates potassium influx into cells through a mechanism regulated by extracellular potassium concentration and intracellular magnesium blockade of outward current. Beyond canonical ion transport, KCNJ15 functions as a tumor suppressor in lung and esophageal cancers. In lung carcinogenesis, KCNJ15 is silenced by DNA hypermethylation and suppresses cell growth, invasion, and migration by activating Hippo pathway YAP phosphorylation through interaction with GNB1 1. In esophageal squamous cell carcinoma, KCNJ15 knockdown significantly reduces cell invasion and proliferation, while high expression paradoxically associates with poor prognosis 2. KCNJ15 also plays roles in neurological disease: a PD-linked R28C mutation causes loss-of-function with dominant-negative effects and impaired plasma membrane trafficking 3, while reduced KCNJ15 expression associates with epilepsy risk, linked to the polymorphism rs2833098 4. Additionally, KCNJ15 is implicated as an Alzheimer's disease susceptibility gene 5 and functions in galvanotaxis by coupling with polyamines to sense weak electric fields 6. A T2DM-associated synonymous variant increases KCNJ15 expression and mRNA stability in Asian populations 7.