Correct regulation of PI metabolism is essential for efficient insulin secretion from β-cells (79). Indeed, PI(4)P is the main precursor to form PI(4,5)P2, which is rapidly turned over to form second messengers required for insulin secretion (68) in a Ca2+-dependent manner akin to the release of neurotransmitters from neurons. Interestingly, a distinct role for PI(4)P in signaling from the plasma membrane in the β-cell has been suggested (80), since PI(4)P displayed antisynchronous oscillations compared with PI(4,5)P2 when MIN6 β-cells were stimulated with glucose. A direct role in secretion has already been shown in yeast (24), and it is well known that PI(4)P is involved in membrane trafficking between the Golgi and the plasma membrane and other endosomal compartments (75). Hence, VPS13C could function in insulin secretion through regulation of PI metabolism, affecting intracellular insulin trafficking.