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DPYSL2

DPYSL2, also known as dihydropyrimidinase-related protein 2, is a protein encoded by the DPYSL2 gene in humans. It belongs to a family of cytosolic phosphoproteins involved in neuronal development and axonal guidance. It is also known by several other names including CRMP2 (collapsin response mediator protein 2), TOAD-64 (turned on after division, 64 kDa), and ULIP-2 (unc-33-like phosphoprotein-2).

DPYSL2 plays a critical role in several cellular processes, particularly in the nervous system. These include:

  • Axonal Guidance: DPYSL2 mediates the repulsive effects of semaphorins on neuronal growth cones, helping to direct axons to their correct targets during development.
  • Neurite Outgrowth: It promotes neurite extension, a crucial step in the formation of neuronal networks.
  • Synaptic Plasticity: DPYSL2 is involved in the structural changes that occur at synapses in response to neuronal activity, contributing to learning and memory.
  • Cell Migration: It influences the movement of cells during development and in response to injury.

DPYSL2 is regulated by phosphorylation, and its activity can be modulated by various kinases and phosphatases. These modifications affect its interaction with other proteins and its subcellular localization. Changes in DPYSL2 phosphorylation have been implicated in several neurological disorders.

Reduced or aberrant DPYSL2 function has been linked to several neurological and psychiatric conditions, including:

  • Alzheimer's Disease: DPYSL2 phosphorylation is altered in Alzheimer's disease, contributing to synaptic dysfunction and neuronal loss.
  • Schizophrenia: Genetic variations in the DPYSL2 gene have been associated with an increased risk of schizophrenia.
  • Bipolar Disorder: DPYSL2 expression levels are altered in individuals with bipolar disorder.
  • Down Syndrome: DPYSL2 is overexpressed in Down syndrome and contributes to the neurological impairments seen in this condition.
  • Neuronal Injury: Following traumatic brain injury or stroke, DPYSL2 phosphorylation is altered, contributing to neuronal damage and functional deficits.

Due to its crucial role in neuronal function and its involvement in various neurological disorders, DPYSL2 is an active area of research, with potential as a therapeutic target.