Exposing a solution to a temperature gradient can lead to the accumulation of particles on either the cold or warm side. This phenomenon is known as thermophoresis, and its microscopic origin is still debated. Here, we show that thermophoresis can be observed in any system having internal states with different transport properties, and temperature-modulated rates of transitions between the states. These internal degrees of freedom might be configurational, chemical or velocity states. We also derive an expression for the Soret coefficient, which decides whether particles accumulate on the cold or warm side. Our framework can be applied to any chemical reaction system diffusing in a temperature gradient. It also captures the possibility to observe a sign inversion of the Soret coefficient as the competition between chemical and velocity states. We establish thermophoresis as a genuine non-equilibrium effect, originating from internal microscopic currents consistent with the necessity of transporting heat from warm to cold regions.