GLI proteins are participants of the evolutionary conserved Hedgehog (Hh) signaling pathway, which plays a key role in the proliferation and differentiation of cells and morphogenesis of particular tissues and organs. Hh signaling pathways activate by binding of Hh ligands to the PTCH transmembranous receptor. In this process SMO activates and that leads to an increased activity of the GLI transcription factors, which support the transcription of target genes. There are three isoforms of the GLI proteins in people GLI1, GLI2, GLI3, which do not have the same function because of the difference in structure. GLI proteins participate in the differentiation of trophoblasts in the development of the placenta. The stem cells of the trophoblast differentiate into cytotrophoblast cells (which play a key role in the creation of the two layers of the placenta), non-migratory villous trophoblast (built of syntitiotrophoblast cells) and an invasive extravillous trophoblast (built of cytotrophoblast cells). These two layers of the placenta differentiate in functions. If a disrupted activation of the Hh signaling pathway and disruption of a normal signaling cascade (and therefore even an aberrant expression of GLI proteins) occurs, a disruption in differentiation of the trophoblasts that leads to different diseases (such as hydatidiform mole, invasive mole, choriocarcinoma, placental site trophoblastic tumour and epitheloid trophoblastic tumour) may occur. The mentioned diseases are characterised by abnormal proliferation of trophoblasts and together make up a group of pathological conditions known as gestational trophoblastic diseases. The connection of the aberrant expression of the GLI proteins along with the development of diseases shows the importance of a standard regulation of transcription factors during the dfferentiation of trophoblasts and a normal development of the placenta.