TBC1D4 and polycystic ovary syndrome: The decrease in insulin sensitivity has been attributed to post-receptor alterations in intracellular signaling pathways of insulin occurring in PCOS (Højlund, 2014); different studies have indeed detected defects in insulin signaling through insulin receptor substrates (IRS-1; Langlais et al., 2011), Akt2 (Tan et al., 2007), PI3K (Cusi et al., 2000), and AS160/TBC1D4 (Larance et al., 2005), which can account for reduced insulin action on glucose transport.