The molecular mechanisms responsible for the downregulation and/or not targeting to the basolateral membrane of NIS in thyroid tumors remain poorly understood, but some studies demonstrated that both mRNA and protein are differentially expressed according to the genetic background of the tumor. In fact, papillary thyroid carcinomas (PTCs) harboring the BRAFV600E mutation present lower SLC5A5 mRNA and NIS protein expression as well as less targeting to the basolateral membrane compared to PTCs BRAFWT (19, 24, 27). Nonetheless, a recent study reported different association between NIS membrane expression and BRAFV600E mutation in a series of 96 cPTCs, demonstrating that the ones harboring BRAFV600E mutation expressed more often NIS in the cell membrane of tumor cells compared to BRAFWT cPTCs (28). Less is known about the impact of mutations in other genes (i.e. RAS and TERTp) on SLC5A5 and NIS expression/targeting to the basolateral membrane.