Dihydropyrimidinase-related protein 2 (DPYSL2)

Dihydropyrimidinase-related protein 2 (DPYSL2), also known as Collapsin Response Mediator Protein 2 (CRMP2), is a cytosolic protein essential for microtubule dynamics and axonal growth (UniProt P63172). It promotes the assembly of tubulin heterodimers into microtubules, thereby facilitating neuronal polarity and neurite outgrowth (PubMed: 12183371). In neurodegenerative disorders like Alzheimer's disease, DPYSL2 is frequently hyperphosphorylated by kinases such as GSK-3β and CDK5, which impairs its ability to stabilize microtubules and leads to synaptic loss (PubMed: 22491973). Beyond its structural role, DPYSL2 regulates the trafficking and activity of N-type voltage-gated calcium channels (CaV2.2), making it a relevant target for chronic pain management (PubMed: 24508565). The anticonvulsant drug lacosamide has been shown to bind to DPYSL2, potentially contributing to its therapeutic effects in epilepsy and pain (PubMed: 20606181). Additionally, DPYSL2 is implicated in cancer progression, where its overexpression is linked to increased cell migration and metastasis (PubMed: 28844807).

Other names

Collapsin response mediator protein 2CRMP2DRP-2ULIP2Unc-33-like phosphoprotein 2Muscular dystrophy-associated protein

Modulation of microtubule stability and regulation of voltage-gated calcium channel activity through direct binding or inhibition of hyperphosphorylation.