The simplest answer is: E is energy, m is mass, and c is the speed of light in a vacuum. But what does this really mean? Well, to be correct, Einstein's full equation is:
E^2 = (mc^2)^2 + (pc)^2,
where p stands for momentum. This equation applies to much more than the colloquial E = mc^2. It applies to moving objects, explains why mass drops when two atoms join together, and many other relativistic observations. Also, a very important point is that, because both sides of the equation are squared, solving for E (energy) yields to answers, a positive one and a negative one. This realization is what led to the hypothesis and eventually the discovery of anti-matter, which posses negative energy and/or mass.
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