Collectively, our findings underscore the concept that Orai1 might be a stress response molecule that is upregulated in cardiac hypertrophy, associated with Pyk2 and/or MEK/ERK cascade overactivation and SERCA2a downregulation, leading to depressed Ca2+ cycling and ventricular dysfunction as part of a maladaptive response. The gene discussed is PTK2B; the disease is cardiac hypertrophy.