We’ve dedicated the past decade to unraveling the intricate role of calcium as a second messenger, critical in balancing life and death within cells. Our research focuses on the calcium release mediated by the inositol 1,4,5-trisphosphate receptor (InsP3R), which plays a pivotal role in the calcium communication between the endoplasmic reticulum (ER) and mitochondria. One of our groundbreaking discoveries show that cancer cells are addicted to this communication and selectively died when it is disrupted. More recently, we discover that senescence cells rewired it calcium tool kit and its ER mitochondrial communication.