[5][6] PKCε is an isoform of the large PKC family of protein kinases that play many roles in different tissues.

[9][20] A myriad of agonists have also been shown to induce the translocation of PKCε from the cytosolic to particulate fraction in cardiomyocytes, including but not limited to PMA or norepinephrine;[9]arachidonic acid;[21]ET-1 and phenylephrine;[22][23] angiotensin II and diastolic stretch;[24] adenosine;[25] hypoxia and Akt-induced stem cell factor;[26] ROS generated via pharmacologic activation of the mitochondrial potassium-sensitive ATP channel (mitoK(ATP))[27] and the endogenous G-protein coupled receptor ligand, apelin.

PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways.

This kinase has been shown to be involved in many different cellular functions, such as apoptosis, cardioprotection from ischemia, heat shock response, as well as insulin exocytosis.

[38] Further support was gained from in vivo studies in which mice expressing a mutant cTnI (Serine43/45Alanine) exhibited enhanced cardiac contractility.

Initially, PKCε was thought to protect mitochondria from MPT through its association with VDAC1, ANT, and hexokinase II;[40] however, genetic studies have since ruled this out[44][45] and subsequent studies have identified the F0/F1 ATP synthase as a core inner mitochondrial membrane component[46][47][48][49] and Bax and Bak as potential outer membrane components[50] These findings have opened up new avenues of investigation for the role of PKCε at mitochondria.

[40] These data suggest that PKCε may act at multiple modulatory targets of MPT function; further studies are required to unveil the specific mechanism.

It was first demonstrated by Ping et al. that in five distinct preconditioning regimens in conscious rabbits, the epsilon isoform of PKC specifically translocated from the cytosolic to particulate fraction.

PKCε has been shown to target and phosphorylate alcohol dehydrogenase 2 (ALDH2) following preconditioning stimuli, which increased the activity of ALDH2 and reduced infarct size.

[81] Lastly, several mitochondrial metabolic targets of PKCε phosphorylation involved in cardioprotection following activation with εRACK have been identified, including mitochondrial respiratory complexes I, II and III, as well as proteins involved in glycolysis, lipid oxidation, ketone body metabolism and heat shock proteins.

PKCε translocation to sarcomeres and phosphorylation of cTnI and cMyBPC is involved in the κ-opioid- and α-adrenergic-dependent preconditioning that slows myosin cycling rate, thus protecting the contractile apparatus from damage.

[82][83] Activation of PKCε by εRACK prior to ischemia was also found to phosphorylate Ventricular myosin light chain-2,[54] however the functional significance remains elusive.

Actin-capping protein, CapZ appears to affect the localization of PKCε to Z-lines[84] and modulates the cardiomyocyte response to ischemic injury.

Knockout and molecular studies in mice suggest that this kinase is important for regulating behavioural response to morphine[86] and alcohol.