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Deubiquitylation errors cause disease

Developmental Biology
Many proteins require reversible modification of ubiquitylation for normal function, and failure of deubiquitylation can cause disease. Beck et al. identified a defect in the X-linked OTUD5 gene and assembled a cohort of male patients with similar phenotype, all with missense variants in OTUD5 . Through an analysis of patient tissues and animal models, they identified a common defect in deubiquitylation and demonstrated that this error impaired neuroectodermal differentiation, a disorder they named LINKED syndrome (linkage-specific-deubiquitinylation-deficiency-induced embryonic defects). This work demonstrates the critical importance of linkage-specific ubiquitin cleavage to the chromatin remodeling process and development.

Sci. Adv. 10.1126/sciadv.abe2116 (2021).