After a brief introduction of the general features of myocardial PLC isozymes, the focus will be on a specific subtype of PLC, PLCβ isoforms, due to their potential contribution to various pathological processes, such as cardiac hypertrophy, diabetic cardiomyopathy (DCM), and myocardial ischemia/reperfusion (I/R) injury (Table 1). Here, HSPG2 is linked to familial dilated cardiomyopathy.