TPC2 in drug development: Emerging target for cancer, viral infections, cardiovascular diseases, and neurological disorders

Abstract

The lysosomal two-pore channel 2 (TPC2) modulates intracellular calcium (Ca^2 +) signaling and has been implicated in inflammatory, cardiovascular, and neurodegenerative conditions, as well as cancer and viral infections. Despite its potential as a drug target, TPC2 is still in the early stages of therapeutic development. The major challenges include achieving high target specificity without inducing unintended effects on other endolysosomal channels and on the crosstalk between TPC2 and other intracellular and extracellular Ca²⁺ channels. Recent advancements in the structural analysis of TPC2, along with the development of TPC2 agonists and inhibitors, have significantly expanded our understanding of its mechanistic contributions to disease. This review highlights potential TPC2-based therapies for cancer, inflammation, and neurological disorders, emphasizing the need for further research to develop targeted TPC2 modulators and fully elucidate the molecular mechanisms of TPC2.