Ubap1, or ubiquitin-associated protein 1, is one of the subunits of the endosomal sorting complex required for transport I (ESCRT-I). It binds to ubiquitin-tagged proteins and plays a crucial role in endosome sorting, linking endosomal trafficking to the ubiquitination machinery pathways [3,4,5].

Conditional disruption of Ubap1 in mice causes severe brain dysplasia and prenatal ventriculomegaly. Ubap1 depletion disrupts adherens junctions and polarity of radial glial cells (RGCs), leading to abnormal interkinetic nuclear migration, reduced neural progenitor cell proliferation, and precocious differentiation [2]. Ubap1+/E176Efx23 knock-in mice, with a heterozygous Ubap1 truncated mutation, develop progressive hind limb dysfunction months after birth, along with spinal cord neuron loss and ubiquitinated protein accumulation, suggesting disturbed endosome-mediated vesicular trafficking [1]. In zebrafish, in vivo down-regulation of Ubap1 causes abnormal morphology, inhibited motor neuron outgrowth, decreased mobility, and shorter lifespan [3].

In conclusion, Ubap1 is essential for endosome sorting and normal neural development. Mouse models with Ubap1 mutations have been instrumental in revealing its role in neurodegenerative disorders like hereditary spastic paraplegia (SPG80), highlighting its significance in understanding the molecular pathogenesis of such diseases and for screening therapeutic agents [1,3].