Dihydropyrimidinase-related protein 2

Dihydropyrimidinase-related protein 2 (DPYSL2, also known as DRP-2) is a 62 kDa cytoplasmic protein involved in neuronal development and polarity (UniProt: Q16555). It plays roles in axon growth and guidance, neuronal growth cone collapse, and cell migration. DPYSL2 is necessary for signaling by class 3 semaphorins and the associated cytoskeletal remodeling, and may also participate in endocytosis (UniProt: Q16555).

DPYSL2 is predominantly expressed in nervous tissues where it regulates axonal architecture and neuronal morphogenesis. No specific disease associations are documented in the UniProt record (UniProt: Q16555).

DPYSL2 is associated with Alzheimer's Disease based on proteomics profiling. Analysis of post-mortem AD brain tissue versus age-matched controls using TMT-labeled quantitative proteomics across four subcellular fractions revealed that DPYSL2 is downregulated in AD brain, with a mean log2 fold-change of −0.32 (Chaparral AD proteomics). This reduction may reflect pathological alterations in axonal integrity and neuronal structural dynamics in AD pathology.