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, playing a crucial role in endosome sorting and is involved in endosomal trafficking pathways. Genetic models, such as knock-in and knockout mice, are valuable for studying Ubap1's function [1,2,3,4].

In Ubap1+/E176Efx23 knock-in mice (a model of SPG80), the animals showed normal appearance at birth but developed progressive hind limb dysfunction later. Molecularly, there was loss of neurons in the spinal cord, accumulation of ubiquitinated proteins, and disrupted endosome-mediated vesicular trafficking, as indicated by changes in Rab5 and Rab7 distributions [1]. Conditional disruption of Ubap1 in mice caused severe brain dysplasia and prenatal ventriculomegaly by disrupting adherens junctions and polarity of radial glial cells, reducing neural progenitor cell proliferation and inducing precocious differentiation [2]. In zebrafish, in vivo down-regulation of Ubap1 led to abnormal morphology, inhibited motor neuron outgrowth, decreased mobility, and shorter lifespan. In cell cultures, patient-derived truncated forms of UBAP1 caused aberrant endosome clustering, enlargement, and cytoplasmic accumulation of ubiquitinated proteins, and disruption of Ubap1 in cultured cortical neurons from transgenic Ubap1flox mice led to dysregulation of early endosome processing and ubiquitinated protein sorting [3].

In conclusion, Ubap1 is essential for endosome sorting and endosomal trafficking. Mouse models, including KO/CKO models, have revealed its significance in neurodegenerative disorders like hereditary spastic paraplegia (such as SPG80) and in brain development, providing insights into the molecular pathogenesis and potential for therapeutic agent screening [1,2,3].