VPS26A functions as a core component of the retromer cargo-selective complex (CSC), which prevents missorting of transmembrane proteins into lysosomal degradation pathways and facilitates retrograde transport from endosomes to the trans-Golgi network 1. The protein plays critical roles in cellular trafficking, including recycling of receptors like mGluR5 through VPS26A-SNX27 interactions, which is implicated in neuropathic pain development 2. VPS26A regulates neurogenesis by interacting with Nox4 signaling and ROS/ERK1/2 pathways, with deficiency suppressing stem cell differentiation 3. In disease contexts, VPS26A levels are reduced in diabetic conditions and amyotrophic lateral sclerosis, where high glucose downregulates VPS26A through ROS/NF-κB-mediated promoter hypermethylation, leading to dysregulated amyloid precursor protein processing and tau phosphorylation 14. Conversely, VPS26A is overexpressed in pancreatic adenocarcinoma and hepatocellular carcinoma, where it promotes tumor progression through EGFR/ERK signaling activation and correlates with poor prognosis 56. Unlike VPS35, mutations in VPS26A are not commonly associated with Parkinson's disease 7. The protein exhibits maternal-zygotic expression patterns during embryonic development and is essential for normal cellular trafficking functions 8.