Roles and regulation of phospholipid scramblases

FEBS Lett. 2015 Jan 2;589(1):3-14. doi: 10.1016/j.febslet.2014.11.036. Epub 2014 Dec 3.


Phospholipid scramblase activity is involved in the collapse of phospholipid (PL) asymmetry at the plasma membrane leading to externalization of phosphatidylserine. This activity is crucial for initiation of the blood coagulation cascade and for recognition/elimination of apoptotic cells by macrophages. Efforts to identify gene products associated with this activity led to the characterization of PL scramblase (PLSCR) and XKR family members which contribute to phosphatidylserine exposure in response to apoptotic stimuli. Meanwhile, TMEM16 family members were identified to externalize phosphatidylserine in response to elevated calcium in Scott syndrome platelets, which is critical for activation of the coagulation cascade. Herein, we report their mechanisms of gene regulation, molecular functions independent of their scrambling activity, and their potential roles in pathogenic conditions.

Keywords: Autoimmunity; Bacterial protection; Cancer; PL scramblase; Phospholipid scramblase; Scott syndrome; Transmembrane protein 16; Viral replication; XK-related protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis*
  • Blood Coagulation Disorders / enzymology*
  • Blood Coagulation Disorders / genetics
  • Blood Coagulation Disorders / pathology
  • Blood Platelets / enzymology*
  • Blood Platelets / pathology
  • Cell Membrane / enzymology*
  • Cell Membrane / genetics
  • Cell Membrane / pathology
  • Humans
  • Phosphatidylserines / genetics
  • Phosphatidylserines / metabolism*
  • Phospholipid Transfer Proteins / genetics
  • Phospholipid Transfer Proteins / metabolism*


  • Phosphatidylserines
  • Phospholipid Transfer Proteins

Supplementary concepts

  • Scott Syndrome