Rebekah Sanchez-Hodge

Domain-dependent uncoupling of the co-chaperone and E3 ubiquitin ligase CHIP underlies heterogeneity in spinocerebellar ataxia 48.

Analysis of SCA48-associated variants spanning the TPR and U-box domains indicates that SCA48 results from domain-specific disruption of CHIP's dual functions, producing varying degrees of CHIP insufficiency and/or gain-of-toxic effects that together contribute to the phenotypic diversity observed across patients.