Protein turnover (PT) has been formally defined only in equilibrium conditions, which is ill-suited to quantify PT during dynamic processes that occur during embryogenesis or (extra) cellular signaling. In this Hypothesis, we propose a definition of PT in an out-of-equilibrium regime that allows the quantification of PT in virtually any biological context. We propose a simple mathematical and conceptual framework applicable to a broad range of available data, such as RNA sequencing coupled with pulsed-SILAC datasets. We apply our framework to a published dataset and show that stimulation of mouse dendritic cells with LPS leads to a proteome-wide change in PT. This is the first quantification of PT out-of-equilibrium, paving the way for the analysis of biological systems in other contexts.