Ca V 1.2 calcium channel is the primary conduit for Ca 2+ influx into cardiac and smooth muscles that underscores its importance in the pathogenesis of hypertension, atherosclerosis, myocardial infarction, and heart failure. But, a few controversies still remain. Therefore, exploring new ways to modulate Ca V 1.2 channel activity will augment the arsenal of Ca V 1.2 channel-based therapeutics for treatment of cardiovascular diseases. Here, we will mainly introduce a couple of emerging Ca V 1.2 channel interacting proteins, such as Galectin-1 and Cereblon, and discuss their roles in hypertension and heart failure through fine-tuning Ca V 1.2 channel activity. Of current interest, we will also evaluate the implication of the role of Ca V 1.2 channel in SARS-CoV-2 infection and the potential treatments of COVID-19-related cardiovascular symptoms.