In search for new prognostic factors, the Pleckstrin homology domain containing S1 (PLEKHS1) gene has attracted our attention, because hotspot PLEKHS1 promoter mutations (Figure 1A) have also been shown to occur in different types of human cancer including TC and other malignancies where TERT promoter mutations are frequently observed [17,18]. This evidence concerns the gene PLEKHS1 and cancer.