{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nVPS50 is a protein uniquely associated with the endosome‐associated recycling protein (EARP) complex, distinguishing it from the related Golgi‐associated retrograde protein (GARP) complex. While EARP and GARP share subunits VPS51, VPS52, and VPS53, VPS50’s presence in EARP is crucial for mediating endocytic recycling, as it facilitates the return of internalized cargo such as the transferrin receptor back to the plasma membrane."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nInvestigations in individuals with biallelic hypomorphic variants in VPS50 revealed profound neurodevelopmental issues, including severe developmental delay, microcephaly, corpus callosum hypoplasia, seizures, and additional systemic manifestations such as transient neonatal cholestasis. In liver tissue, the mislocalization of gamma‐glutamyltransferase from bile canaliculi to basolateral membranes, along with aberrant tight junction formation, underscores VPS50’s role in maintaining cell polarity and proper membrane trafficking in hepatocytes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the cellular level, patient‐derived fibroblasts exhibited reduced levels of VPS50 accompanied by decreased VPS52 and VPS53, highlighting the interdependency within the EARP complex. Although the internalization rate of the transferrin receptor remained unaltered, its recycling to the plasma membrane was significantly delayed, emphasizing VPS50’s critical role in endocytic receptor recycling. These findings consolidate the concept that VPS50 is essential not only for endocytic recycling but also for the establishment of cell polarity and the regulation of trafficking between basolateral and apical membranes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pauline E Schneeberger, Sheela Nampoothiri, Tess Holling, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic variants in VPS50 cause a neurodevelopmental disorder with neonatal cholestasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awab206"}], "href": "https://doi.org/10.1093/brain/awab206"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34037727"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34037727"}]}]}]}