TXNDC15 modulated quality control at the endoplasmic reticulum shapes ciliogenesis

TXNDC15 regulates ER membrane protein quality control by tuning MARCHF6, and patient TXNDC15 mutations linked to Meckel-Gruber syndrome disrupt ciliogenesis.

• Why it matters: ER quality control must prevent excess or mislocalized membrane subunits from accumulating, but how this tuning shapes cilia formation and ciliopathy risk is unclear.
• What they did: Genome-wide CRISPR screens identified TXNDC15, and follow-up experiments showed it modulates MARCHF6 to enhance ubiquitination and degradation of soluble cytosolic-domain subunits while blocking lumenal-domain misrecruitment.
• The result: Meckel-Gruber–causing TXNDC15 mutations disrupted TXNDC15–MARCHF6 binding, permitting degradation of critical ciliary proteins during ER transit and producing ciliogenesis defects.

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