FBXL21 regulates diurnal proteostasis in skeletal muscle by targeting DNAJB6 and client proteins.

FBXL21 controls diurnal proteostasis in skeletal muscle by degrading DNAJB6 and its client proteins, with mutations conferring resistance and disrupting protein balance.

• Why it matters: Understanding circadian regulation of muscle proteostasis is crucial because it impacts muscle health and disease, yet the underlying mechanisms are poorly characterized.
• What they did: The study used genetic and biochemical approaches, including knockout and mutant models, to show that FBXL21 ubiquitinates DNAJB6 and proteins like Desmin and TDP-43, affecting their degradation and accumulation.
• The result: Disruption of FBXL21 leads to abnormal protein buildup and impaired diurnal rhythms, which can be rescued by muscle-specific FBXL21 expression, suggesting a therapeutic target for myopathies.