In 2015, PMCA4b (plasma membrane ATPase) was discovered to bind with renalase and activate the aforementioned signaling pathways [27], thus rekindling the search for the causative interplay of renalase and CVD, as PMCA4b is connected to both cardiac hypertrophy [28] and hypertension [29]. This evidence concerns the gene ATP2B4 and cardiac hypertrophy.