Dihydropyrimidinase-related protein 5 (DPYSL5)

Dihydropyrimidinase-related protein 5 (DPYSL5, CRMP5) is an intracellular member of the collapsin response mediator protein family that orchestrates brain development by regulating cytoskeletal structure, neuronal migration, axon guidance, and dendritic growth. It acts through interactions with microtubules, MAP2, and βIII-tubulin, forming protein complexes essential for neuronal connectivity and morphogenesis. Functional mutations in DPYSL5 lead to cerebral malformations and intellectual disability. Its expression is upregulated in various neuroendocrine cancers, where it promotes stemness, lineage plasticity, and therapy resistance—particularly in prostate cancer. DPYSL5 is also a paraneoplastic autoantigen in certain neurologic syndromes. The protein negatively regulates dendritic outgrowth and can induce mitophagy in neurons. While no direct drugs target DPYSL5, it is implicated in cancer progression and as a diagnostic marker for paraneoplastic neurological disorders. Targeting this molecule therapeutically must be approached cautiously due to its essential roles in neural development and maintenance.

Other names

CRMP5ULIP6DRP-5CRAMCV2UNC33-like phosphoprotein 6collapsin response mediator protein 5CRMP3-associated moleculeRTSC4Ulip6CRMP-5

Drug-induced modulation: Antiandrogens (e.g., Enzalutamide) can upregulate DPYSL5, contributing to neuroendocrine lineage plasticity and therapy resistance in prostate cancer. Immunotherapy: Paraneoplastic autoantibodies to DPYSL5/CRMP5 are used for diagnosis of paraneoplastic syndromes, but not as therapeutics.