In this article, we review the role of endolysosomal cation channels in cancer, particularly the association between TPC2 and key pathophysiological processes involved in cancer development, to uncover the roles of TPC2 in different stages of cancer from tumor initiation to tumor cell migration as well as its potential as a novel hallmark of tumors and a druggable target for future cancer therapy. This evidence concerns the gene TPCN2 and cancer.