Genes encoding heterologous proteins are introduced into the plant genome for several purposes. First, the plant‐made protein can be a tool in fundamental research. Second, the synthesis of heterologous proteins in plants can have biotechnological applications. Plants are capable of producing several types of recombinant proteins. Indeed, for the production of all these proteins, the use of plants is obvious, because they have several important advantages; plants can grow easily and inexpensively in large quantities and they can be harvested and processed with the available agronomic infrastructures and upscaling is very simple. Finally, using processes similar to those used in food and feed industry, specifically desired proteins can be easily purified. However, the stability of accumulation is as important as the accumulation levels themselves. Indeed, the introduced transgenes are not always correctly expressed and are often susceptible to position effects and homology‐dependent gene silencing (HDGS) mechanisms. Although the mechanism that induces silencing is still not completely unravelled, already some factors are defined which influence transgene expression, such as copy number and chromosomal position, methylation pattern in the integration region and properties of the transgene sequence itself.