ABSTRACT
The genome is no longer deemed as a fixed and inert item but rather as a moldable matter that is continuously evolving and adapting. Within this frame, Transposable Elements (TEs), ubiquitous, mobile, repetitive elements, are considered an alive portion of the genomes to date, whose functions, although long considered "dark", are now coming to light. Here we will review that, besides the detrimental effects that TE mobilization can induce, TEs have shaped genomes in their current form, promoting genome sizing, genomic rearrangements and shuffling of DNA sequences. Although TEs are mostly represented in the genomes by evolutionarily old, short, degenerated, and sedentary fossils, they have been thoroughly co-opted by the hosts as a prolific and original source of regulatory instruments for the control of gene transcription and genome organization in the nuclear space. For these reasons, the deregulation of TE expression and/or activity is implicated in the onset and progression of several diseases. It is likely that we have just revealed the outermost layers of TE functions. Further studies on this portion of the genome are required to unlock novel regulatory functions that could also be exploited for diagnostic and therapeutic approaches.