In this study, we report that Kir2.1 is preferentially expressed by non-WNT/SHH MBs and contributes to tumor progression by recruiting disintegrin and metalloproteinase domain-containing protein 10 (Adam10) to enhance S2 cleavage of Notch2, thereby activating the Notch2 pathway. The gene discussed is KCNJ2; the disease is neoplasm.